SOX7

Chr 8

SRY-box transcription factor 7

NCBI Gene: 83595 ENSG00000171056 UniProt: Q9BT81

SOX7 encodes a transcription factor that binds DNA to regulate gene expression during embryonic development, particularly activating genes in blood vessel endothelium and repressing Wnt signaling pathways. Pathogenic variants cause a neurodevelopmental disorder with intellectual disability, developmental delay, and multiple congenital anomalies, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.619), consistent with its role in early development.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The protein may play a role in tumorigenesis. A similar protein in mice is involved in the regulation of the wingless-type MMTV integration site family (Wnt) pathway. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Limited · congenital heart disease · AD · ClinGen 2024

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

—

Mechanism

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?

0.62LOEUF

pLI 0.479

Z-score 2.37

OE 0.20 (0.08–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.74Z-score

OE missense 1.13 (1.03–1.25)

289 obs / 255.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.20 (0.08–0.62)

0≤0.351.4

Missense OE?1.13 (1.03–1.25)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 2 / 10.2Missense obs/exp: 289 / 255.5Syn Z: -2.29

Background carrier burden — how many people carry a rare variant somewhere in SOX7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

749 rare PASS variants

Rare truncating (LoF)

1 in 6,700

56 rare PASS variants

Rare synonymous (reference)

1 in 110

344 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SOX7. 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 130	1 in 7,900
South Asian	~43k	1 in 82	1 in 4,600
Remaining (unassigned)	~30k	1 in 96	1 in 5,800
European (Finnish)	~27k	1 in 390	1 in 2,600
Admixed American	~22k	1 in 82	1 in 2,200
African / African American	~21k	1 in 78	≈ 1 in 14,000
East Asian	~20k	1 in 130	≈ 1 in 6,300
Ashkenazi Jewish	~13k	1 in 590	none seen
Middle Eastern	~2,884	1 in 99	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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓