HDGFL3

Chr 15

HDGF like 3

Also known as: CGI-142, HDGF-2, HDGF2, HDGFRP3, HRP-3

NCBI Gene: 50810 ENSG00000166503 UniProt: Q9Y3E1 OMIM: 616643

This protein binds microtubules and enhances DNA synthesis, contributing to microtubule polymerization and neuron projection development. The gene is highly constrained against loss-of-function variants (pLI = 0.97), but no specific disease associations have been established in the provided data. Inheritance pattern is not determined from the available information.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable microtubule binding activity. Predicted to be involved in microtubule polymerization; negative regulation of microtubule depolymerization; and neuron projection development. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.27

Clinical Summary— HDGFL3

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

36 VUS of 52 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.974

Z-score 3.10

OE 0.00 (0.00–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.57Z-score

OE missense 0.56 (0.45–0.70)

57 obs / 101.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.27)

0≤0.351.4

Missense OE?0.56 (0.45–0.70)

0≤0.61.4

Synonymous OE?0.70

0≤1.21.6

LoF obs/exp: 0 / 11.2Missense obs/exp: 57 / 101.7Syn Z: 1.46

This gene — mechanism propensity

0.3892th %ile

GOF

0.2696th %ile

LOF

0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS36

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	35	0	36
Likely Benign	0	0	1	1
Benign	0	0	0	0
Total	1	35	1	37

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap HDGFL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →