MTPAP

mitochondrial poly(A) polymerase, the group of Terminal nucleotidyltransferases|Non-canonical poly(A) polymerases

Basic information

Region (hg38): 10:30309801-30374448

Previous symbols: [ "PAPD1" ]

Links

ENSG00000107951 ∙ NCBI:55149 ∙ OMIM:613669 ∙ HGNC:25532 ∙ Uniprot:Q9NVV4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spastic ataxia 4 (Strong), mode of inheritance: AR
• spastic ataxia 4 (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic ataxia 4, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20970105; 25008111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTPAP gene.

• Spastic ataxia 4 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTPAP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	69	2	73
missense	1	1	145	5	2	154
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			7	10	1	18
non coding			3	46	25	74
Total	1	1	155	120	29

Highest pathogenic variant AF is 0.0000131

Variants in MTPAP

This is a list of pathogenic ClinVar variants found in the MTPAP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-30313463-C-T			Likely benign (Jul 07, 2018)
10-30313622-C-T		not specified	Conflicting classifications of pathogenicity (Dec 15, 2023)
10-30313626-T-C		Inborn genetic diseases	Likely benign (Jan 31, 2022)
10-30313631-C-G			Uncertain significance (Jun 28, 2022)
10-30313640-C-T			Uncertain significance (Aug 07, 2022)
10-30313661-G-A		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
10-30313665-T-C			Uncertain significance (Sep 21, 2022)
10-30313670-C-G			Uncertain significance (Oct 03, 2022)
10-30313680-A-G			Uncertain significance (Feb 25, 2022)
10-30313682-T-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
10-30313685-A-G		Spastic ataxia 4	Uncertain significance (Feb 23, 2020)
10-30313686-G-A			Likely benign (Feb 27, 2022)
10-30313691-T-G		Inborn genetic diseases	Uncertain significance (May 22, 2023)
10-30313694-T-C			Uncertain significance (Mar 10, 2022)
10-30313715-T-G			Uncertain significance (Aug 13, 2024)
10-30313718-T-C		not specified	Conflicting classifications of pathogenicity (Apr 11, 2022)
10-30313721-C-T		not specified • MTPAP-related disorder	Benign/Likely benign (Jan 22, 2024)
10-30313730-T-G		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
10-30313734-T-C			Uncertain significance (Apr 23, 2024)
10-30313745-C-G		Inborn genetic diseases	Uncertain significance (Nov 02, 2023)
10-30313746-T-G			Likely benign (Aug 10, 2022)
10-30313751-G-C		not specified	Conflicting classifications of pathogenicity (Jan 14, 2024)
10-30313752-G-C			Uncertain significance (Apr 11, 2022)
10-30313759-T-C			Likely benign (Dec 25, 2023)
10-30313761-G-A			Uncertain significance (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTPAP	protein_coding	protein_coding	ENST00000263063	9	64648

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000955	125738	0	9	125747	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	263	310	0.848	0.0000170	3816
Missense in Polyphen		43	85.972	0.50016		1114
Synonymous	-0.628	125	116	1.07	0.00000635	1134
Loss of Function	4.40	1	24.6	0.0407	0.00000136	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. Can use all four nucleotides, but has higher activity with ATP and UTP (in vitro). Plays a role in replication-dependent histone mRNA degradation. May be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated. Might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA. {ECO:0000269|PubMed:15547249, ECO:0000269|PubMed:15769737, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:20970105, ECO:0000269|PubMed:21292163}.
• Pathway: Purine metabolism (Consensus)

Recessive Scores

• pRec: 0.0734

Intolerance Scores

• loftool: 0.448
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.36

Haploinsufficiency Scores

• pHI: 0.0821
• hipred: Y
• hipred_score: 0.543
• ghis: 0.542

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mtpap

Gene ontology

• Biological process: mRNA polyadenylation;histone mRNA catabolic process
• Cellular component: mitochondrion;intracellular membrane-bounded organelle
• Molecular function: magnesium ion binding;UTP binding;RNA binding;polynucleotide adenylyltransferase activity;protein binding;ATP binding;manganese ion binding;identical protein binding;protein homodimerization activity