SIPA1L2

protein-coding

signal induced proliferation associated 1 like 2, the group of PDZ domain containing

Gene summary

This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

MANE transcript

NM_020808.5

Inheritance

—

ClinVar variants

U:257B:22

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr1:232,397,965-232,630,571

External References & Databases

Ensembl (ENSG00000116991)

Transcript & Mutation Effects

hg38 • Region Span ~232.6 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 SIPA1L2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 249

not providedTotal: 15

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020808.5. 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			5 clinvar	3 clinvar	8 clinvar	16
missense			246 clinvar	10 clinvar	1 clinvar	257
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	257	13	9	279

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 98 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020808.5	RefSeq	NP_065859.3	21	MANE Select
ENST00000674635.1	Ensembl	ENSP00000502693.1	21	MANE Select
NM_001377488.1	RefSeq	NP_001364417.1	20	Standard
ENST00000308942.4	Ensembl	ENSP00000309102.4	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Rap1 signaling pathway - Homo sapiens (human)

Biological Process

biological_process
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366630
Coding exons: 21
Length: 163594
Individuals with no LoFs: 124986
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125006
p: 0.0000800

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	877	1.01e+3	0.870	0.0000600	11314
Missense (PolyPhen)		316	433.19	0.72947		4921
Synonymous	-1.01	446	420	1.06	0.0000284	3421
Loss of Function	6.60	14	76.2	0.184	0.00000460	829

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.134
RVIS EVS: -1.31
RVIS percentile EVS: 4.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.224

Gene Damage Prediction

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