HAPLN1

protein-coding

hyaluronan and proteoglycan link protein 1, the group of V-set domain containing

Gene summary

Predicted to enable hyaluronic acid binding activity. Predicted to be an extracellular matrix structural constituent conferring compression resistance. Predicted to be involved in central nervous system development and skeletal system development. Located in extracellular matrix. Is active in gel phase of interstitial matrix. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

CRTL1

MANE transcript

NM_001884.4

Inheritance

—

ClinVar variants

U:50B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr5:83,637,805-83,720,855

External References & Databases

Ensembl (ENSG00000145681)

Transcript & Mutation Effects

hg38 • Region Span ~83.1 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 HAPLN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001884.4. 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		2
missense			48 clinvar	1 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	50	2	0	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001884.4	RefSeq	NP_001875.1	4	MANE Select
ENST00000274341.9	Ensembl	ENSP00000274341.4	4	MANE Select
ENST00000503117.1	Ensembl	ENSP00000426610.1	3	Standard
ENST00000504713.5	Ensembl	ENSP00000422522.2	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hapln1b	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: hypoplastic abnormal

Gene / Model

Organism

Observed Phenotype

hapln1b

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: hypoplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular matrix organization
ECM proteoglycans

Biological Process

skeletal system development
cell adhesion
central nervous system development
extracellular matrix organization

Molecular Function

hyaluronic acid binding
extracellular matrix structural constituent conferring compression resistance

Cellular Component

extracellular region
extracellular matrix
synapse
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274341
Coding exons: 4
Length: 83809
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125736
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.414	182	198	0.917	0.0000112	2294
Missense (PolyPhen)		63	85.288	0.73867		857
Synonymous	-1.06	90	78.1	1.15	0.00000454	692
Loss of Function	3.00	3	15.9	0.189	9.02e-7	172

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix.;

Recessive Scores

pRec: 0.185

Intolerance Scores

LoFtool: 0.341
RVIS EVS: -0.54
RVIS percentile EVS: 20.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.946

Gene Damage Prediction

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