SOX11

Chr 2AD

SRY-box transcription factor 11

Also known as: CSS9, IDDMOH, MRD27

NCBI Gene: 6664 ENSG00000176887 UniProt: P35716 OMIM: 600898

SOX11 encodes a transcription factor that binds to gene promoters to activate transcription and plays a critical role in cell survival during development of the neural tube, branchial arches, and somites. Mutations cause autosomal dominant intellectual developmental disorder with microcephaly and variable features including ocular malformations or hypogonadotropic hypogonadism. The gene is highly constrained against loss-of-function variants, reflecting its essential role in neurodevelopment.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This intronless 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 function in the developing nervous system and play a role in tumorigenesis. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadismMIM #615866

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · SOX11-related complex neurodevelopmental disorder with or without congenital anomalies · AD · ClinGen 2025

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

108

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — SOX11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.858

Z-score 2.76

OE 0.09 (0.03–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.26Z-score

OE missense 0.59 (0.52–0.68)

146 obs / 245.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.44)

0≤0.351.4

Missense OE?0.59 (0.52–0.68)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 1 / 10.8Missense obs/exp: 146 / 245.6Syn Z: -2.95

Background carrier burden — how many people carry a rare variant somewhere in SOX11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

532 rare PASS variants

Rare truncating (LoF)

1 in 41,000

13 rare PASS variants

Rare synonymous (reference)

1 in 180

384 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SOX11. 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 290	1 in 68,000
South Asian	~43k	1 in 170	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 170	none seen
European (Finnish)	~27k	1 in 290	≈ 1 in 6,300
Admixed American	~22k	1 in 300	≈ 1 in 11,000
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 230	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 10,000
Middle Eastern	~2,884	1 in 360	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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓