SMAP1

protein-coding

small ArfGAP 1, the group of ArfGAPs

Gene summary

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]

MANE transcript

NM_001044305.3

Inheritance

—

ClinVar variants

P:1U:63B:2

Top phenotype

Developmental and epileptic encephalopathy, 54

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr6:70,667,776-70,862,011

External References & Databases

Ensembl (ENSG00000112305)

Transcript & Mutation Effects

hg38 • Region Span ~194.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMAP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 2

Developmental and epileptic encephalopathy, 54Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001044305.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			62 clinvar	1 clinvar		63
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	1	0	63	2	0	66

Highest pathogenic variant AF is 0.0000069983994

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001044305.3	RefSeq	NP_001037770.1	11	MANE Select
ENST00000370455.8	Ensembl	ENSP00000359484.3	11	MANE Select
NM_001281439.2	RefSeq	NP_001268368.1	11	Standard
NM_001281440.1	RefSeq	NP_001268369.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

positive regulation of GTPase activity
positive regulation of erythrocyte differentiation
regulation of clathrin-dependent endocytosis

Molecular Function

GTPase activator activity
clathrin binding
metal ion binding

Cellular Component

cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370455
Coding exons: 11
Length: 194240
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125745
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	193	241	0.801	0.0000112	3035
Missense (PolyPhen)		44	80.899	0.54389		1042
Synonymous	-0.457	91	85.6	1.06	0.00000445	905
Loss of Function	4.15	2	23.8	0.0839	0.00000115	281

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000038	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activating protein that acts on ARF6. Plays a role in clathrin-dependent endocytosis. May play a role in erythropoiesis (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.521
RVIS EVS: -0.07
RVIS percentile EVS: 48.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.380

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium