SYP

Chr XXLR

synaptophysin

Also known as: MRX96, MRXSYP, XLID96

NCBI Gene: 6855 ENSG00000102003 UniProt: P08247 OMIM: 313475

This gene encodes synaptophysin, an integral membrane protein of synaptic vesicles that regulates synaptic plasticity and directs targeting of synaptobrevin to intracellular compartments. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.39), indicating that complete loss of function is likely not tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells. The protein also binds cholesterol and is thought to direct targeting of vesicle-associated membrane protein 2 (synaptobrevin) to intracellular compartments. Mutations in this gene are associated with an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 96MIM #300802

XLR

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · non-syndromic X-linked intellectual disability · XL · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

200

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

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

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 370

231 rare PASS variants

Rare truncating (LoF)

1 in 33,000

8 rare PASS variants

Rare synonymous (reference)

1 in 300

153 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SYP. 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 420	1 in 110,000
South Asian	~36k	1 in 340	1 in 1,700
Remaining (unassigned)	~31k	1 in 340	≈ 1 in 29,000
European (Finnish)	~27k	1 in 710	≈ 1 in 27,000
Admixed American	~23k	1 in 610	none seen
African / African American	~21k	1 in 420	≈ 1 in 5,600
East Asian	~20k	1 in 320	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 1,800	none seen
Middle Eastern	~2,758	1 in 390	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.