RFC3

Chr 13

replication factor C subunit 3

Also known as: RFC38

NCBI Gene: 5983 ENSG00000133119 UniProt: P40938

RFC3 encodes the 38 kDa subunit of replication factor C (RFC), which loads proliferating cell nuclear antigen (PCNA) onto primed DNA during DNA replication by polymerases delta and epsilon. Biallelic RFC3 mutations cause autosomal recessive immunodeficiency with severe combined immunodeficiency (SCID) phenotype, reflecting the critical role of DNA replication in rapidly dividing immune cells. The gene shows minimal constraint against loss-of-function variants in the general population (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kDa. This gene encodes the 38 kDa subunit. This subunit is essential for the interaction between the 140 kDa subunit and the core complex that consists of the 36, 37, and 40 kDa subunits. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.75

OE 0.57 (0.36–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.13Z-score

OE missense 1.03 (0.91–1.16)

196 obs / 191.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.36–0.94)

0≤0.351.4

Missense OE?1.03 (0.91–1.16)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 11 / 19.3Missense obs/exp: 196 / 191.0Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in RFC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

467 rare PASS variants

Rare truncating (LoF)

1 in 1,200

83 rare PASS variants

Rare synonymous (reference)

1 in 220

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RFC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 360	1 in 1,000
South Asian	~43k	1 in 110	1 in 2,100
Remaining (unassigned)	~30k	1 in 210	1 in 2,400
European (Finnish)	~27k	1 in 480	1 in 3,800
Admixed American	~22k	1 in 130	1 in 1,500
African / African American	~21k	1 in 150	1 in 1,100
East Asian	~20k	1 in 150	1 in 1,400
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 4,100
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 9 coding exons well covered in gnomAD exomes; exons 3, 4, 7, 8 marginal. Genomes: all 9.? see exons ↓