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 presynaptic modulation of chemical synaptic transmission; 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, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.49

Clinical Summary— TPRG1L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

40 VUS of 54 total submissions

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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

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

VUS40

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	40	40
Likely Benign	4	4
Benign	0	0
Total	44	44

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

View in ClinVar →

93 pathogenic / likely-pathogenic (of 109) ClinVar copy-number / structural variants overlap TPRG1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →