SYAP1

Chr X

synapse associated protein 1

Also known as: BSTA, PRO3113, SAP47

NCBI Gene: 94056 ENSG00000169895 UniProt: Q96A49 OMIM: 301161

The SYAP1 protein promotes mTORC2-mediated phosphorylation of AKT1 and plays a role in adipocyte differentiation and cellular responses to growth factors. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.35), indicating that complete loss of function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Involved in several processes, including TORC2 signaling; cellular response to epidermal growth factor stimulus; and cellular response to peptide hormone stimulus. Located in several cellular components, including Golgi apparatus; cytoplasmic side of plasma membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

0.35

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.35LOEUF

pLI 0.943

Z-score 3.15

OE 0.07 (0.03–0.35)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.16Z-score

OE missense 0.71 (0.60–0.85)

90 obs / 126.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.35)

0≤0.351.4

Missense OE?0.71 (0.60–0.85)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 13.5Missense obs/exp: 90 / 126.7Syn Z: 0.34

Background carrier burden — how many people carry a rare variant somewhere in SYAP1?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

233 rare PASS variants

Rare truncating (LoF)

1 in 36,000

8 rare PASS variants

Rare synonymous (reference)

1 in 480

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SYAP1. 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)	~561k	1 in 380	1 in 27,000
South Asian	~36k	1 in 230	≈ 1 in 17,000
Remaining (unassigned)	~31k	1 in 270	none seen
European (Finnish)	~27k	1 in 5,300	none seen
Admixed American	~23k	1 in 510	≈ 1 in 20,000
African / African American	~21k	1 in 350	≈ 1 in 15,000
East Asian	~20k	1 in 220	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 3,200	none seen
Middle Eastern	~2,758	1 in 550	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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓