HAPLN1

Chr 5

hyaluronan and proteoglycan link protein 1

Also known as: CRT1, CRTL1

NCBI Gene: 1404 ENSG00000145681 UniProt: P10915 OMIM: 115435

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.602

Z-score 3.00

OE 0.19 (0.09–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.41Z-score

OE missense 0.92 (0.81–1.04)

182 obs / 198.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.49)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 3 / 15.9Missense obs/exp: 182 / 198.4Syn Z: -1.06

Background carrier burden — how many people carry a rare variant somewhere in HAPLN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

442 rare PASS variants

Rare truncating (LoF)

1 in 8,600

28 rare PASS variants

Rare synonymous (reference)

1 in 150

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HAPLN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 25,000
South Asian	~43k	1 in 180	≈ 1 in 13,000
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 29,000
European (Finnish)	~27k	1 in 1,300	≈ 1 in 8,900
Admixed American	~22k	1 in 150	1 in 2,500
African / African American	~21k	1 in 200	≈ 1 in 4,800
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 670	none seen
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓