HNRNPM

protein-coding

heterogeneous nuclear ribonucleoprotein M, the group of Heterogeneous nuclear ribonucleoproteins|RNA binding motif containing

Gene summary

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNAs. This protein also constitutes a monomer of the N-acetylglucosamine-specific receptor which is postulated to trigger selective recycling of immature GlcNAc-bearing thyroglobulin molecules. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Previous symbols:

NAGR1
HNRPM

MANE transcript

NM_005968.5

Inheritance

—

ClinVar variants

U:105B:5

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:8,444,767-8,489,114

External References & Databases

Ensembl (ENSG00000099783)

Transcript & Mutation Effects

hg38 • Region Span ~44.3 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 HNRNPM variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 6

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005968.5. 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			1 clinvar	1 clinvar	3 clinvar	5
missense			92 clinvar	1 clinvar		93
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	105	2	3	110

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005968.5	RefSeq	NP_005959.2	16	MANE Select
ENST00000325495.9	Ensembl	ENSP00000325376.2	16	MANE Select
NM_001297418.2	RefSeq	NP_001284347.1	11	Standard
NM_031203.4	RefSeq	NP_112480.2	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in squamous cell - TarBase

Biological Process

alternative mRNA splicing, via spliceosome
mRNA splicing, via spliceosome
fibroblast growth factor receptor signaling pathway
RNA metabolic process
regulation of mRNA stability involved in response to oxidative stress

Molecular Function

RNA binding
mRNA binding
protein binding
protein domain specific binding

Cellular Component

nucleus
nucleoplasm
spliceosomal complex
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325495
Coding exons: 16
Length: 44348
Individuals with no LoFs: 125643
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125645
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.74	300	467	0.643	0.0000303	4801
Missense (PolyPhen)		44	102.34	0.42995		1145
Synonymous	-1.15	175	157	1.12	0.0000111	1394
Loss of Function	5.24	0	32.0	0.00	0.00000180	373

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000038	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.374
RVIS EVS: -1.4
RVIS percentile EVS: 4.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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