SMAP1

Chr 6

small ArfGAP 1

Also known as: SMAP-1

NCBI Gene: 60682 ENSG00000112305 UniProt: Q8IYB5 OMIM: 611372

This gene encodes a GTPase activating protein that regulates ARF6 and participates in clathrin-dependent endocytosis, with potential roles in erythropoiesis. The gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.26), but no established Mendelian disease associations have been reported to date.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.26

Clinical Summary— SMAP1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 69 VUS of 87 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.994

Z-score 4.15

OE 0.08 (0.03–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.10Z-score

OE missense 0.80 (0.71–0.90)

193 obs / 240.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.26)

0≤0.351.4

Missense OE?0.80 (0.71–0.90)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 2 / 23.8Missense obs/exp: 193 / 240.9Syn Z: -0.46

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS69

Likely Benign2

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	0	69	0	69
Likely Benign	0	1	1	2
Benign	0	1	0	1
Total	1	71	1	73

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap SMAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →