DIPK1A

Chr 1

divergent protein kinase domain 1A

Also known as: FAM69A

NCBI Gene: 388650 ENSG00000154511 UniProt: Q5T7M9 OMIM: 614542

This gene encodes a cysteine-rich transmembrane protein that localizes to the endoplasmic reticulum, though its specific cellular function remains unknown. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically with onset in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.494), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq

This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

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· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.584

Z-score 2.97

OE 0.19 (0.09–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.26Z-score

OE missense 0.56 (0.49–0.66)

120 obs / 212.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.49)

0≤0.351.4

Missense OE?0.56 (0.49–0.66)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 3 / 15.7Missense obs/exp: 120 / 212.6Syn Z: 0.72

Background carrier burden — how many people carry a rare variant somewhere in DIPK1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

444 rare PASS variants

Rare truncating (LoF)

1 in 2,600

92 rare PASS variants

Rare synonymous (reference)

1 in 240

184 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DIPK1A. 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 260	1 in 2,600
South Asian	~43k	1 in 190	1 in 1,600
Remaining (unassigned)	~30k	1 in 120	1 in 3,600
European (Finnish)	~27k	1 in 520	≈ 1 in 6,100
Admixed American	~22k	1 in 160	1 in 1,800
African / African American	~21k	1 in 170	1 in 2,300
East Asian	~20k	1 in 150	1 in 1,000
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,883	1 in 260	≈ 1 in 2,600

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): 2 of 5 coding exons well covered in gnomAD exomes; exons 1, 2, 3 marginal. Genomes: all 5.? see exons ↓