PDILT

Chr 16

protein disulfide isomerase like, testis expressed

Also known as: PDIA7

The protein is a redox-inactive chaperone specifically expressed in the testis that is involved in spermatogenesis and belongs to the protein disulfide isomerase family in the endoplasmic reticulum. Mutations cause autosomal recessive male infertility due to multiple morphological abnormalities of the flagella (MMAF), a condition affecting sperm motility and structure. This gene shows very low constraint against loss-of-function variants in the general population, which is consistent with its specialized reproductive function.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.80
Clinical SummaryPDILT
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.30
OE 0.50 (0.320.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.40Z-score
OE missense 1.06 (0.971.16)
342 obs / 322.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.320.80)
00.351.4
Missense OE1.06 (0.971.16)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 12 / 24.2Missense obs/exp: 342 / 322.0Syn Z: -1.21
DN
0.73top 25%
GOF
0.76top 25%
LOF
0.1598th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDILT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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