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: 402381ENSG00000165643UniProt: Q5JUK2OMIM: 610224

The protein is a transcription regulator essential for germline differentiation in both males and females, suppressing genes involved in spermatogonial stem cell maintenance while inducing spermatogonial differentiation genes, and coordinating oocyte differentiation. Mutations cause ovarian dysgenesis in females and spermatogenic failure leading to nonobstructive azoospermia in males, typically presenting during reproductive years when fertility issues become apparent. The gene shows both autosomal recessive and autosomal dominant inheritance patterns depending on the specific mutation and phenotype.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAR/ADLOEUF 0.812 OMIM phenotypes
Clinical Summary— SOHLH1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 78 VUS of 176 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.002
Z-score 2.11
OE 0.43 (0.24–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.72Z-score
OE missense 1.13 (1.02–1.25)
276 obs / 244.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.43 (0.24–0.81)
0≤0.351.4
Missense OE1.13 (1.02–1.25)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 7 / 16.2Missense obs/exp: 276 / 244.2Syn Z: -1.78
DN
0.6454th %ile
GOF
0.5758th %ile
LOF
0.3746th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic6
VUS78
Likely Benign20
Benign10
Conflicting2
56
Pathogenic
6
Likely Pathogenic
78
VUS
20
Likely Benign
10
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
55
0
56
Likely Pathogenic
3
1
2
0
6
VUS
0
65
13
0
78
Likely Benign
0
12
1
7
20
Benign
0
5
4
1
10
Conflicting
—2
Total483758172

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients