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SOHLH1

Chr 9ARAD

spermatogenesis and oogenesis specific basic helix-loop-helix 1

Also known as: C9orf157, NOHLH, ODG5, SPATA27, SPGF32, TEB2, bA100C15.3, bHLHe80

NCBI Gene: 402381 ENSG00000165643 UniProt: Q5JUK2

This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 9. Mutations in this gene are associated with nonobstructive azoospermia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

Ovarian dysgenesis 5MIM #617690

AR

Spermatogenic failure 32MIM #618115

AD

176

ClinVar variants

62

Pathogenic / LP

0.00

pLI score

0

Active trials

Clinical Summary— SOHLH1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

62 Pathogenic / Likely Pathogenic· 77 VUS of 176 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.81LOEUF

pLI 0.002

Z-score 2.11

OE 0.43 (0.24–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.72Z-score

OE missense 1.13 (1.02–1.25)

276 obs / 244.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.24–0.81)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (1.02–1.25)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21

0≤1.21.6

LoF obs/exp: 7 / 16.2Missense obs/exp: 276 / 244.2Syn Z: -1.78

ClinVar Variant Classifications

176 submitted variants in ClinVar

Classification Summary

Pathogenic56

Likely Pathogenic6

VUS77

Likely Benign20

Benign10

Conflicting2

56

Pathogenic

6

Likely Pathogenic

77

VUS

20

Likely Benign

10

Benign

2

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	56	0	56
Likely Pathogenic	1	1	4	0	6
VUS	0	64	13	0	77
Likely Benign	0	12	1	7	20
Benign	0	5	4	1	10
Conflicting	—				2
Total	1	82	78	8	171

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SOHLH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

SPERMATOGENESIS- AND OOGENESIS-SPECIFIC BASIC HELIX-LOOP-HELIX PROTEIN 1; SOHLH1

MIM #610224 · *

Ovarian dysgenesis 5

Molecular basis of disorder known

Autosomal recessive

Spermatogenic failure 32

Molecular basis of disorder known

Autosomal dominant

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Villarroel CE et al.·Reprod Sci

2024Case report

Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency.

Zhao S et al.·Fertil Steril

2015

The mutation c.346-1G > A in SOHLH1 impairs sperm production in the homozygous but not in the heterozygous condition.

Liu M et al.·Hum Mol Genet

2022

Mutations in SOHLH1 gene associate with nonobstructive azoospermia.

Choi Y et al.·Hum Mutat

2010

Homozygous loss-of-function mutations in SOHLH1 in patients with nonsyndromic hypergonadotropic hypogonadism.

Bayram Y et al.·J Clin Endocrinol Metab

2015Case report

Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations.

Nakamura S et al.·Andrology

2017Cohort

Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure.

Cannarella R et al.·Asian J Androl

2021Cohort

Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease.

Jolly A et al.·J Clin Endocrinol Metab

2019Cohort

Identification of Multiple Gene Mutations Accounts for a new Genetic Architecture of Primary Ovarian Insufficiency.

Bouilly J et al.·J Clin Endocrinol Metab

2016

Whole-exome sequencing identifies rare recessive variants in azoospermia patients from consanguineous Pakistani families.

Uddin I et al.·Mol Genet Genomics

2024Cohort

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

[Polyphyllin VII inhibits osteosarcoma xenograft growth in mice by inducing ferroptosis via upregulating SOHLH1].

Xiao D et al.·Nan Fang Yi Ke Da Xue Xue Bao

2025

Sohlh1 Modulates the Stemness and Differentiation of Glioma Stem-Like Cells by Inactivation of Wnt/β-Catenin Signalling Pathway via SFRP1.

Zhi S et al.·J Cell Mol Med

2025🔓 Open Access

Clinical phenotype and genetic analysis of patients with severe oligoasthenospermia carrying heterozygous SOHLH1 c.346-1G>A mutation.

Wen X et al.·Front Genet

2025🔓 Open AccessCohort

Sohlh1 and Lhx8 are prominent biomarkers to estimate the primordial follicle pool in mice.

Liu L et al.·Reprod Biol Endocrinol

2023🔓 Open Access

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)