MTPAP

Chr 10AR

mitochondrial poly(A) polymerase

Also known as: PAPD1, SPAX4, TENT6

NCBI Gene: 55149 ENSG00000107951 UniProt: Q9NVV4 OMIM: 613669

The protein is a polymerase that creates the 3' poly(A) tail of mitochondrial transcripts and is involved in replication-dependent histone mRNA degradation. Mutations cause spastic ataxia 4, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.193), suggesting that biallelic variants are required for disease.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the DNA polymerase type-B-like family. This enzyme synthesizes the 3' poly(A) tail of mitochondrial transcripts and plays a role in replication-dependent histone mRNA degradation.[provided by RefSeq, Jan 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.191 OMIM phenotype

Clinical Summary— MTPAP

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 192 VUS of 445 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MTPAP

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.40

OE 0.04 (0.01–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.95Z-score

OE missense 0.85 (0.77–0.94)

263 obs / 310.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 1 / 24.6Missense obs/exp: 263 / 310.1Syn Z: -0.63

ClinVar Variant Classifications

445 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS192

Likely Benign179

Benign49

Conflicting12

Pathogenic

Likely Pathogenic

192

VUS

179

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	1	1	0	0	2
VUS	9	173	8	2	192
Likely Benign	0	6	86	87	179
Benign	0	2	43	4	49
Conflicting	—				12
Total	10	183	137	93	435

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap MTPAP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →