SNAP29

Chr 22AR

synaptosome associated protein 29

Also known as: CEDNIK, SNAP-29

NCBI Gene: 9342 ENSG00000099940 UniProt: O95721 OMIM: 604202

The SNAP29 protein is a SNARE that mediates membrane fusion events, particularly autophagosome-lysosome fusion during autophagy and membrane fusions required for ciliogenesis. Biallelic mutations cause cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, a multisystem disorder affecting the brain, peripheral nerves, and skin with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants in the general population (high LOEUF score), suggesting complete loss of function may be required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking steps. Two other members of this gene family, SNAP23 and SNAP25, encode proteins that bind a syntaxin protein and mediate synaptic vesicle membrane docking and fusion to the plasma membrane. The protein encoded by this gene binds tightly to multiple syntaxins and is localized to intracellular membrane structures rather than to the plasma membrane. While the protein is mostly membrane-bound, a significant fraction of it is found free in the cytoplasm. Use of multiple polyadenylation sites has been noted for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.861 OMIM phenotype

Clinical Summary— SNAP29

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 164 VUS of 362 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.014

Z-score 1.91

OE 0.41 (0.21–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.87Z-score

OE missense 1.20 (1.06–1.36)

178 obs / 148.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.21–0.86)

0≤0.351.4

Missense OE?1.20 (1.06–1.36)

0≤0.61.4

Synonymous OE?0.74

0≤1.21.6

LoF obs/exp: 5 / 12.2Missense obs/exp: 178 / 148.1Syn Z: 1.52

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSNAP29-related cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK syndrome)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.83top 10%

GOF

0.77top 25%

LOF

0.1697th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

362 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic13

VUS164

Likely Benign126

Benign35

Conflicting9

Pathogenic

Likely Pathogenic

164

VUS

126

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	1	0	12
Likely Pathogenic	10	2	1	0	13
VUS	1	86	77	0	164
Likely Benign	0	5	54	67	126
Benign	0	2	31	2	35
Conflicting	—				9
Total	22	95	164	69	359

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

361 pathogenic / likely-pathogenic (of 430) ClinVar copy-number / structural variants overlap SNAP29 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →