INSRR

protein-coding

insulin receptor related receptor, the group of Receptor tyrosine kinases|Fibronectin type III domain containing

Gene summary

Enables transmembrane receptor protein tyrosine kinase activity. Involved in actin cytoskeleton organization and cellular response to alkaline pH. Part of signaling receptor complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014215.3

Inheritance

—

ClinVar variants

U:182B:43

Top phenotype

Hereditary insensitivity to pain with anhidrosis

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr1:156,840,063-156,859,117

External References & Databases

Ensembl (ENSG00000027644)

Transcript & Mutation Effects

hg38 • Region Span ~19.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INSRR variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 178

not providedTotal: 51

Hereditary insensitivity to pain with anhidrosisTotal: 7

Familial medullary thyroid carcinomaTotal: 3

NTRK1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014215.3. 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			2 clinvar	27 clinvar	3 clinvar	32
missense			177 clinvar	13 clinvar		190
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	182	40	3	225

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014215.3	RefSeq	NP_055030.1	22	MANE Select
ENST00000368195.4	Ensembl	ENSP00000357178.3	22	MANE Select
ENST00001114408.1	Ensembl	ENSP00000784213.1	5	Standard
ENST00001141611.1	Ensembl	ENSP00000809372.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of actin cytoskeleton - Homo sapiens (human)
Prostate cancer - Homo sapiens (human)
Pathways Affected in Adenoid Cystic Carcinoma

Biological Process

transmembrane receptor protein tyrosine kinase signaling pathway
insulin receptor signaling pathway
peptidyl-tyrosine phosphorylation
male sex determination
actin cytoskeleton reorganization

Molecular Function

transmembrane receptor protein tyrosine kinase activity
insulin-activated receptor activity
ATP binding
phosphatidylinositol 3-kinase binding
insulin receptor substrate binding

Cellular Component

integral component of plasma membrane
insulin receptor complex
axon
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368195
Coding exons: 22
Length: 18956
Individuals with no LoFs: 125559
Homozygous LoFs: 0
Heterozygous LoFs: 189
Defined: 125748
p: 0.000752

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.801	740	804	0.920	0.0000491	8355
Missense (PolyPhen)		321	342.39	0.93752		3607
Synonymous	0.0186	333	333	0.999	0.0000204	2725
Loss of Function	1.87	45	60.7	0.741	0.00000312	629

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00064	0.00062	rare
Latino/Admixed American	0.00054	0.00052	rare
Ashkenazi Jewish	0.00017	0.000099	rare
East Asian	0.0011	0.0011	notable
Finnish	0.0015	0.0015	notable
European (Non-Finnish)	0.00076	0.00075	rare
South Asian	0.00053	0.00052	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. {ECO:0000269|PubMed:21641549}.;

Recessive Scores

pRec: 0.196

Intolerance Scores

LoFtool: 0.239
RVIS EVS: -2.25
RVIS percentile EVS: 1.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.688

Gene Damage Prediction

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