TPRG1L

Chr 1

tumor protein p63 regulated 1 like

Also known as: FAM79A, SVAP30, TPRGL, h-mover, mover

NCBI Gene: 127262 ENSG00000158109 UniProt: Q5T0D9 OMIM: 611460

The protein regulates synaptic transmission by decreasing calcium sensitivity of neurotransmitter release at presynapses. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in early childhood. This gene shows low constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable calmodulin binding activity and identical protein binding activity. Predicted to be involved in regulation of glutamatergic synaptic transmission and regulation of synaptic vesicle exocytosis. Predicted to act upstream of or within calcineurin-NFAT signaling cascade; negative regulation of synaptic transmission; and synaptic vesicle docking. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.49LOEUF

pLI 0.000

Z-score 0.37

OE 0.88 (0.54–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.80 (0.68–0.95)

98 obs / 122.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.54–1.49)

0≤0.351.4

Missense OE?0.80 (0.68–0.95)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 10 / 11.4Missense obs/exp: 98 / 122.4Syn Z: -1.37

Background carrier burden — how many people carry a rare variant somewhere in TPRG1L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

380 rare PASS variants

Rare truncating (LoF)

1 in 2,000

84 rare PASS variants

Rare synonymous (reference)

1 in 410

197 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TPRG1L. 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 340	1 in 2,600
South Asian	~43k	1 in 220	1 in 1,800
Remaining (unassigned)	~30k	1 in 220	1 in 2,000
European (Finnish)	~27k	1 in 900	1 in 430
Admixed American	~22k	1 in 180	1 in 520
African / African American	~21k	1 in 160	1 in 760
East Asian	~20k	1 in 300	1 in 1,100
Ashkenazi Jewish	~13k	≈ 1 in 6,500	1 in 930
Middle Eastern	~2,884	1 in 170	1 in 410

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