HMMR

protein-coding

hyaluronan mediated motility receptor, the group of CD molecules

Gene summary

The protein encoded by this gene is involved in cell motility. It is expressed in breast tissue and together with other proteins, it forms a complex with BRCA1 and BRCA2, thus is potentially associated with higher risk of breast cancer. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Dec 2008]

MANE transcript

NM_001142556.2

Inheritance

—

ClinVar variants

P:2U:115B:10

Top phenotype

Familial cancer of breast

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr5:163,460,203-163,491,941

External References & Databases

Ensembl (ENSG00000072571)

Transcript & Mutation Effects

hg38 • Region Span ~31.7 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 HMMR variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 95

Familial cancer of breastTotal: 15

not providedTotal: 5

Ovarian cancerTotal: 4

Breast cancer, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142556.2. 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		3
missense		2 clinvar	100 clinvar	4 clinvar	4 clinvar	110
nonsense			2 clinvar		1 clinvar	3
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	2	115	5	5	127

Highest pathogenic variant AF is 0.000011842463

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142556.2	RefSeq	NP_001136028.1	18	MANE Select
ENST00000393915.9	Ensembl	ENSP00000377492.4	18	MANE Select
NM_001142557.2	RefSeq	NP_001136029.1	15	Standard
NM_012484.3	RefSeq	NP_036616.2	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ECM-receptor interaction - Homo sapiens (human)
Hyaluronan uptake and degradation
Hyaluronan metabolism
Metabolism of carbohydrates
Glycosaminoglycan metabolism

Biological Process

regulation of G2/M transition of mitotic cell cycle
hyaluronan catabolic process

Molecular Function

protein binding
hyaluronic acid binding

Cellular Component

centrosome
cytosol
plasma membrane
cell surface
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393915
Coding exons: 18
Length: 31739
Individuals with no LoFs: 124996
Homozygous LoFs: 15
Heterozygous LoFs: 736
Defined: 125747
p: 0.00299

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.550	299	327	0.914	0.0000154	4774
Missense (PolyPhen)		101	105.25	0.95963		1666
Synonymous	0.815	109	120	0.906	0.00000576	1215
Loss of Function	0.934	35	41.5	0.843	0.00000177	584

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0027	0.0026	notable
Latino/Admixed American	0.0012	0.0011	notable
Ashkenazi Jewish	0.055	0.051	notable
East Asian	0.00045	0.00044	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00098	0.00095	rare
South Asian	0.00051	0.00049	rare
Other	0.0067	0.0062	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for hyaluronic acid (HA) (By similarity). Involved in cell motility (By similarity). When hyaluronan binds to HMMR, the phosphorylation of a number of proteins, including PTK2/FAK1 occurs. May also be involved in cellular transformation and metastasis formation, and in regulating extracellular- regulated kinase (ERK) activity. May act as a regulator of adipogenisis (By similarity). {ECO:0000250|UniProtKB:Q00547}.;

Recessive Scores

pRec: 0.276

Intolerance Scores

LoFtool: 0.998
RVIS EVS: 2.29
RVIS percentile EVS: 98.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.487

Gene Damage Prediction

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