SOHLH2

Chr 13

spermatogenesis and oogenesis specific basic helix-loop-helix 2

Also known as: SOSF2, SPATA28, TEB1, bHLHe81

NCBI Gene: 54937ENSG00000120669UniProt: Q9NX45OMIM: 616066

This gene encodes a transcription factor that regulates germline differentiation in both males and females, suppressing spermatogonial stem cell maintenance genes while inducing differentiation genes in males, and coordinating oocyte differentiation in females. The gene is highly constrained against loss-of-function variants (LOEUF 0.61), suggesting mutations are likely to cause significant clinical effects. Based on the available data, mutations in this gene would be expected to primarily affect reproductive development and fertility.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.61
Clinical Summary— SOHLH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 25 VUS of 90 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
0.61LOEUF
pLI 0.001
Z-score 3.12
OE 0.36 (0.22–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.03Z-score
OE missense 0.82 (0.73–0.92)
212 obs / 258.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.22–0.61)
0≤0.351.4
Missense OE0.82 (0.73–0.92)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 10 / 27.8Missense obs/exp: 212 / 258.7Syn Z: 0.22
DN
0.6551th %ile
GOF
0.5465th %ile
LOF
0.3744th %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

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
VUS25
Likely Benign12
Benign3
49
Pathogenic
25
VUS
12
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
0
0
0
VUS
0
23
2
0
25
Likely Benign
0
6
2
4
12
Benign
0
1
0
2
3
Total03053689

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

View in ClinVar →

Protein Context — Lollipop Plot

SOHLH2 · 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 4 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