CCDC174

protein-coding

coiled-coil domain containing 174

Gene summary

The protein encoded by this gene is found in the nucleus, where it interacts with eukaryotic translation initiation factor 4A, isoform 3. The encoded protein appears to be a part of the exon junction complex, which is involved in RNA processing, translation, and nonsense-mediated mRNA decay. A mutation in this gene has been associated with infantile hypotonia with psychomotor retardation. [provided by RefSeq, Mar 2016]

Previous symbols:

C3orf19

MANE transcript

NM_016474.5

Inheritance

ClinVar variants

U:81B:25

Top phenotype

Hypotonia, infantile, with psychomotor retardation

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr3:14,651,762-14,672,659

External References & Databases

Ensembl (ENSG00000154781)

Transcript & Mutation Effects

hg38 • Region Span ~20.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014784

Submitter: Orphanet

severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014784

Submitter: Ambry Genetics

severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014784

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypotonia, infantile, with psychomotor retardationAR

Manifestation: Cardiovascular; Genitourinary; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management

Refs: 26358778

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC174 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 25

Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndromeTotal: 8

CCDC174-related disorderTotal: 5

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016474.5. 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	13 clinvar		15
missense			77 clinvar	9 clinvar	3 clinvar	89
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	81	22	3	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016474.5	RefSeq	NP_057558.3	11	MANE Select
ENST00000383794.7	Ensembl	ENSP00000373304.3	11	MANE Select
NM_001410719.1	RefSeq	NP_001397648.1	9	Standard
ENST00000303688.8	Ensembl	ENSP00000302344.7	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000383794
Coding exons: 11
Length: 20896
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0441	259	261	0.992	0.0000145	3080
Missense (PolyPhen)		32	34.319	0.93244		374
Synonymous	-0.217	92	89.4	1.03	0.00000495	839
Loss of Function	2.13	16	28.2	0.568	0.00000160	327

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00024	0.00023	rare
South Asian	0.00052	0.00049	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably involved in neuronal development. {ECO:0000269|PubMed:26358778}.;

Recessive Scores

pRec: 0.0979

Intolerance Scores

RVIS EVS: 0.09
RVIS percentile EVS: 60.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E

Gene Damage Prediction

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