HAPLN4

protein-coding

hyaluronan and proteoglycan link protein 4, the group of V-set domain containing

Gene summary

Predicted to be a structural constituent of synapse-associated extracellular matrix. Predicted to be involved in GABAergic synaptic transmission; nervous system development; and skeletal system development. Predicted to be active in obsolete extracellular space; perineuronal net; and synapse. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_023002.3

Inheritance

—

ClinVar variants

U:66B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr19:19,254,756-19,262,804

External References & Databases

Ensembl (ENSG00000187664)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 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 HAPLN4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023002.3. 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	2
missense			66 clinvar			66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	66	0	2	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023002.3	RefSeq	NP_075378.1	5	MANE Select
ENST00000291481.8	Ensembl	ENSP00000291481.5	5	MANE Select
ENST00000898464.1	Ensembl	ENSP00000568523.1	5	Standard
ENST00000898464.2	Ensembl	ENSP00000568523.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

skeletal system development
cell adhesion
central nervous system development

Molecular Function

hyaluronic acid binding

Cellular Component

extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291481
Coding exons: 5
Length: 7156
Individuals with no LoFs: 125577
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125613
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.73	192	273	0.704	0.0000203	2454
Missense (PolyPhen)		88	116.03	0.75842		1020
Synonymous	1.91	103	131	0.787	0.0000107	899
Loss of Function	2.31	6	15.9	0.376	9.46e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.0015	0.0014	notable
East Asian	0.00051	0.00049	rare
Finnish	0.000057	0.000046	rare
European (Non-Finnish)	0.000033	0.000026	rare
South Asian	0.00016	0.00016	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to hyaluronic acid and may be involved in formation of the extracellular matrix. {ECO:0000250|UniProtKB:Q80WM4}.;

Recessive Scores

pRec: 0.114

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.235

Gene Damage Prediction

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