IGSF21

protein-coding

immunoglobin superfamily member 21, the group of V-set domain containing

Gene summary

This gene encodes a protein which has two immunoglobulin (Ig) domains and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Sep 2011]

MANE transcript

NM_032880.5

Inheritance

—

ClinVar variants

U:94B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr1:18,107,798-18,378,483

External References & Databases

Ensembl (ENSG00000117154)

Transcript & Mutation Effects

hg38 • Region Span ~270.7 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 IGSF21 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032880.5. 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			3 clinvar		1 clinvar	4
missense			89 clinvar	3 clinvar	2 clinvar	94
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	94	3	3	100

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032880.5	RefSeq	NP_116269.3	10	MANE Select
ENST00000251296.4	Ensembl	ENSP00000251296.1	10	MANE Select
ENST00000873157.1	Ensembl	ENSP00000543216.1	8	Standard
ENST00000873157.2	Ensembl	ENSP00000543216.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

homophilic cell adhesion via plasma membrane adhesion molecules
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
synapse maturation

Molecular Function

signaling receptor activity
protein homodimerization activity
cell adhesion molecule binding

Cellular Component

cell-cell adherens junction
anchored component of external side of plasma membrane
presynaptic membrane
postsynaptic membrane
inhibitory synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251296
Coding exons: 10
Length: 270738
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.324	296	312	0.948	0.0000215	2998
Missense (PolyPhen)		125	139.36	0.89697		1216
Synonymous	0.265	129	133	0.971	0.00000961	1004
Loss of Function	3.11	5	20.0	0.249	0.00000102	221

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2. {ECO:0000250|UniProtKB:Q7TNR6}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.336
RVIS EVS: -0.6
RVIS percentile EVS: 18.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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