CCDC6

protein-coding

coiled-coil domain containing 6

Gene summary

This gene encodes a coiled-coil domain-containing protein. The encoded protein is ubiquitously expressed and may function as a tumor suppressor. A chromosomal rearrangement resulting in the expression of a fusion gene containing a portion of this gene and the intracellular kinase-encoding domain of the ret proto-oncogene is the cause of thyroid papillary carcinoma.[provided by RefSeq, Sep 2010]

Previous symbols:

TST1
D10S170

MANE transcript

NM_005436.5

Inheritance

—

ClinVar variants

U:40B:3

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr10:59,788,747-59,906,556

External References & Databases

Ensembl (ENSG00000108091)

Transcript & Mutation Effects

hg38 • Region Span ~117.8 kb

Loading mutation effect viewer...

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 CCDC6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 3

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005436.5. 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			38 clinvar		1 clinvar	39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	40	0	3	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005436.5	RefSeq	NP_005427.2	9	MANE Select
ENST00000263102.7	Ensembl	ENSP00000263102.6	9	MANE Select
ENST00000862752.1	Ensembl	ENSP00000532811.1	9	Standard
ENST00000862752.2	Ensembl	ENSP00000532811.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pathways in cancer - Homo sapiens (human)
Thyroid cancer - Homo sapiens (human)
Retinoblastoma (RB) in Cancer
Mesodermal Commitment Pathway

Biological Process

cytoskeleton organization
biological_process

Molecular Function

structural constituent of cytoskeleton
protein binding
SH3 domain binding

Cellular Component

cytosol
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263102
Coding exons: 9
Length: 117894
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125746
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.81	144	275	0.523	0.0000151	3087
Missense (PolyPhen)		15	77.374	0.19386		1010
Synonymous	0.815	102	113	0.902	0.00000660	914
Loss of Function	3.64	5	24.4	0.205	0.00000129	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000075	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Note=A chromosomal aberration involving CCDC6 is found in papillary thyroid carcinomas (PTCs). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene. {ECO:0000269|PubMed:2406025}.;

Recessive Scores

pRec: 0.167

Intolerance Scores

LoFtool: 0.178
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.691

Gene Damage Prediction

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