CHTF18

protein-coding

chromosome transmission fidelity factor 18, the group of AAA ATPases

Gene summary

This gene encodes a protein which is a component of a replication factor C (RFC) complex, which loads proliferating cell nuclear antigen (PCNA) on to DNA during the S phase of cell cycle. The encoded protein may interact with other proteins, including RFC complex 3, to form a clamp loader complex that plays a role in sister chromatid cohesion during metaphase-anaphase transition. [provided by RefSeq, Jan 2016]

Previous symbols:

C16orf41

MANE transcript

NM_022092.3

Inheritance

—

ClinVar variants

U:308B:32

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr16:788,046-800,737

External References & Databases

Ensembl (ENSG00000127586)

Transcript & Mutation Effects

hg38 • Region Span ~12.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHTF18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 311

not providedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022092.3. 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			5 clinvar	3 clinvar	6 clinvar	14
missense			297 clinvar	19 clinvar	4 clinvar	320
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	308	22	10	340

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022092.3	RefSeq	NP_071375.1	22	MANE Select
ENST00000262315.14	Ensembl	ENSP00000262315.9	22	MANE Select
ENST00000317063.10	Ensembl	ENSP00000313029.7	22	Standard
ENST00000426047.1	Ensembl	ENSP00000412015.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric Cancer Network 2

Biological Process

DNA replication
cell cycle
positive regulation of DNA-directed DNA polymerase activity

Molecular Function

DNA clamp loader activity
protein binding
ATP binding
single-stranded DNA-dependent ATPase activity

Cellular Component

nucleoplasm
cytosol
membrane
Ctf18 RFC-like complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262315
Coding exons: 22
Length: 12692
Individuals with no LoFs: 124136
Homozygous LoFs: 0
Heterozygous LoFs: 139
Defined: 124275
p: 0.000559

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.79	895	628	1.43	0.0000451	6059
Missense (PolyPhen)		252	196.49	1.2825		1908
Synonymous	-8.93	457	270	1.69	0.0000190	2045
Loss of Function	0.617	45	49.7	0.906	0.00000293	488

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00051	0.00045	rare
Latino/Admixed American	0.00051	0.00049	rare
Ashkenazi Jewish	0.00011	0.00010	rare
East Asian	0.0021	0.0020	notable
Finnish	0.00020	0.00019	rare
European (Non-Finnish)	0.00052	0.00049	rare
South Asian	0.00060	0.00056	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single- stranded and primed DNAs and has weak ATPase activity that is stimulated by the presence of primed DNA, replication protein A (RPA) and by proliferating cell nuclear antigen (PCNA). The CTF18- RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. It also interacts with and stimulates DNA polymerase POLH. {ECO:0000269|PubMed:12766176, ECO:0000269|PubMed:12930902, ECO:0000269|PubMed:17545166}.;

Recessive Scores

pRec: 0.255

Intolerance Scores

RVIS EVS: 1.08
RVIS percentile EVS: 91.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.747

Gene Damage Prediction

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