POLA2

protein-coding

DNA polymerase alpha 2, accessory subunit, the group of DNA polymerases

Gene summary

Predicted to enable DNA binding activity. Involved in DNA replication initiation and DNA replication, synthesis of primer. Located in nucleoplasm. Part of alpha DNA polymerase:primase complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_002689.4

Inheritance

ClinVar variants

P:4U:83B:1

Top phenotype

telomere syndrome

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr11:65,261,913-65,305,959

External References & Databases

Ensembl (ENSG00000014138)

Transcript & Mutation Effects

hg38 • Region Span ~44.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

telomere syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100137

Submitter: Ambry Genetics

telomere syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100137

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POLA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 77

Telomere Biology DisorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002689.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense		2 clinvar	77 clinvar	1 clinvar		80
nonsense			2 clinvar			2
start loss	1 clinvar					1
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	2	2	83	1	0	88

Highest pathogenic variant AF is 0.00003181094

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002689.4	RefSeq	NP_002680.2	18	MANE Select
ENST00000265465.8	Ensembl	ENSP00000265465.3	18	MANE Select
NM_001437761.1	RefSeq	NP_001424690.1	17	Standard
NM_001438747.1	RefSeq	NP_001425676.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
DNA replication - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

G1/S transition of mitotic cell cycle
DNA replication
DNA replication initiation
telomere maintenance via semi-conservative replication
DNA biosynthetic process

Molecular Function

molecular_function
DNA binding
DNA-directed DNA polymerase activity
protein heterodimerization activity

Cellular Component

nucleoplasm
alpha DNA polymerase:primase complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265465
Coding exons: 18
Length: 43828
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	278	332	0.837	0.0000176	3857
Missense (PolyPhen)		78	100.24	0.77812		1138
Synonymous	0.189	137	140	0.980	0.00000857	1206
Loss of Function	3.29	17	39.2	0.434	0.00000225	421

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00026	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an essential role at the early stage of chromosomal DNA replication by coupling the polymerase alpha/primase complex to the cellular replication machinery. {ECO:0000250}.;

Recessive Scores

pRec: 0.269

Intolerance Scores

LoFtool: 0.705
RVIS EVS: -0.78
RVIS percentile EVS: 12.97

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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