SOHLH2

Chr 13

spermatogenesis and oogenesis specific basic helix-loop-helix 2

Also known as: SOSF2, SPATA28, TEB1, bHLHe81

NCBI Gene: 54937 ENSG00000120669 UniProt: Q9NX45

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.

ResearchSummary from RefSeq, UniProt

This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 13. The proteins encoded by this gene and another testis-specific transcription factor, SOHLH1, can form heterodimers, in addition to homodimers. There is a read-through locus (GeneID: 100526761) that shares sequence identity with this gene and the upstream CCDC169 (GeneID: 728591). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.36 (0.22–0.61)

0≤0.351.4

Missense OE?0.82 (0.73–0.92)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 10 / 27.8Missense obs/exp: 212 / 258.7Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in SOHLH2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

444 rare PASS variants

Rare truncating (LoF)

1 in 2,700

49 rare PASS variants

Rare synonymous (reference)

1 in 410

204 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SOHLH2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 5,900
South Asian	~43k	1 in 86	1 in 3,800
Remaining (unassigned)	~30k	1 in 100	1 in 2,400
European (Finnish)	~27k	1 in 380	1 in 3,000
Admixed American	~22k	1 in 140	1 in 700
African / African American	~21k	1 in 120	≈ 1 in 6,400
East Asian	~20k	1 in 210	1 in 3,000
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 180	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓