SALL4

Chr 20AD

spalt like transcription factor 4

Also known as: DRRS, HSAL4, IVIC, ZNF797

NCBI Gene: 57167 ENSG00000101115 UniProt: Q9UJQ4 OMIM: 607343

This gene encodes a zinc finger transcription factor essential for maintaining and renewing embryonic and hematopoietic stem cells. Mutations cause Duane-radial ray syndrome and IVIC syndrome, both presenting with characteristic eye movement abnormalities (Duane anomaly) and limb malformations affecting the radial ray. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variation, indicating critical developmental importance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger transcription factor thought to play a role in the development of abducens motor neurons. Defects in this gene are a cause of Duane-radial ray syndrome (DRRS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?IVIC syndromeMIM #147750

Duane-radial ray syndromeMIM #607323

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Duane-radial ray syndrome; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

152

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — SALL4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 5.04

OE 0.00 (0.00–0.10)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.08Z-score

OE missense 0.88 (0.82–0.94)

539 obs / 614.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.88 (0.82–0.94)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 0 / 29.5Missense obs/exp: 539 / 614.0Syn Z: -2.39

Background carrier burden — how many people carry a rare variant somewhere in SALL4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,263 rare PASS variants

Rare truncating (LoF)

1 in 4,700

25 rare PASS variants

Rare synonymous (reference)

1 in 49

613 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SALL4. 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 55	1 in 4,000
South Asian	~43k	1 in 63	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 49	1 in 5,000
European (Finnish)	~27k	1 in 120	1 in 2,200
Admixed American	~22k	1 in 51	1 in 3,700
African / African American	~21k	1 in 38	none seen
East Asian	~20k	1 in 49	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 160	none seen
Middle Eastern	~2,884	1 in 49	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓