FLT4

Chr 5

fms related receptor tyrosine kinase 4

Also known as: CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL, VEGFR-3, VEGFR3

NCBI Gene: 2324 ENSG00000037280 UniProt: P35916

This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLymphatic malformation 1

UniProtHemangioma, capillary infantile

UniProtCongenital heart defects, multiple types, 7

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — FLT4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 7.28

OE 0.07 (0.04–0.15)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.83Z-score

OE missense 0.73 (0.68–0.78)

626 obs / 859.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.15)

0≤0.351.4

Missense OE?0.73 (0.68–0.78)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 5 / 71.4Missense obs/exp: 626 / 859.8Syn Z: -1.77

Background carrier burden — how many people carry a rare variant somewhere in FLT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 30

1,645 rare PASS variants

Rare truncating (LoF)

1 in 3,100

86 rare PASS variants

Rare synonymous (reference)

1 in 49

924 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FLT4. 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 56	1 in 1,200
South Asian	~43k	1 in 28	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 34	≈ 1 in 7,500
European (Finnish)	~27k	1 in 83	1 in 1,300
Admixed American	~22k	1 in 27	1 in 2,200
African / African American	~21k	1 in 30	1 in 1,900
East Asian	~20k	1 in 33	1 in 930
Ashkenazi Jewish	~13k	1 in 89	none seen
Middle Eastern	~2,884	1 in 30	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): 29 of 30 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 30.? see exons ↓