SIRPG

protein-coding

signal regulatory protein gamma, the group of V-set domain containing|CD molecules|Ig-like cell adhesion molecule family|C1-set domain containing|Signal regulatory proteins

Gene summary

The protein encoded by this gene is a member of the signal-regulatory protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Previous symbols:

SIRPB2

MANE transcript

NM_018556.4

Inheritance

ClinVar variants

U:64B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.23

Max pathogenic AF

—

Genomic locus

chr20:1,629,152-1,657,779

External References & Databases

Ensembl (ENSG00000089012)

Transcript & Mutation Effects

hg38 • Region Span ~28.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a LOF variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Limited with total score of 4. Single variant segregation (3 points), experimental evidence: testicular expression (1 points) (PMID: 27965440).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIRPG variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018556.4. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			60 clinvar	9 clinvar		69
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	64	10	1	75

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018556.4	RefSeq	NP_061026.2	5	MANE Select
ENST00000303415.7	Ensembl	ENSP00000305529.3	5	MANE Select
NM_001039508.2	RefSeq	NP_001034597.1	4	Standard
NM_080816.3	RefSeq	NP_543006.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Osteoclast differentiation - Homo sapiens (human)
Cell surface interactions at the vascular wall
Hemostasis
Signal regulatory protein family interactions
Cell-Cell communication

Biological Process

cell adhesion
cell-cell signaling
positive regulation of cell population proliferation
negative regulation of cell population proliferation
positive regulation of cell-cell adhesion

Molecular Function

protein binding

Cellular Component

plasma membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303415
Coding exons: 5
Length: 28628
Individuals with no LoFs: 125407
Homozygous LoFs: 1
Heterozygous LoFs: 340
Defined: 125748
p: 0.00136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.272	229	218	1.05	0.0000122	2478
Missense (PolyPhen)		45	44.053	1.0215		617
Synonymous	-0.877	100	89.5	1.12	0.00000536	809
Loss of Function	-0.849	20	16.3	1.23	8.55e-7	171

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0018	0.0017	notable
Latino/Admixed American	0.0019	0.0019	notable
Ashkenazi Jewish	0.0014	0.0014	notable
East Asian	0.00016	0.00016	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.0018	0.0018	notable
South Asian	0.000065	0.000065	rare
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable immunoglobulin-like cell surface receptor. On binding with CD47, mediates cell-cell adhesion. Engagement on T- cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation and costimulates T-cell activation. {ECO:0000269|PubMed:15383453}.;

Recessive Scores

pRec: 0.0864

Intolerance Scores

LoFtool: 0.925
RVIS EVS: 0.8
RVIS percentile EVS: 87.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.108

Gene Damage Prediction

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