CC2D1A

coiled-coil and C2 domain containing 1A, the group of C2 domain containing

Basic information

Region (hg38): 19:13906201-13930879

Links

ENSG00000132024 ∙ NCBI:54862 ∙ OMIM:610055 ∙ HGNC:30237 ∙ Uniprot:Q6P1N0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 3 (Moderate), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AR
• intellectual disability, autosomal recessive 3 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16033914; 17149387

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CC2D1A gene.

• not_provided (484 variants)
• Inborn_genetic_diseases (285 variants)
• Intellectual_disability,_autosomal_recessive_3 (66 variants)
• not_specified (58 variants)
• CC2D1A-related_disorder (33 variants)
• Intellectual_disability (5 variants)
• Ciliopathy (2 variants)
• Smith-Magenis_Syndrome-like (2 variants)
• Cerebral_palsy (1 variants)
• Autosomal_recessive_non-syndromic_intellectual_disability (1 variants)
• Visual_impairment (1 variants)
• Global_developmental_delay (1 variants)
• Premature_ovarian_failure_19 (1 variants)
• Autism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CC2D1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017721.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	171	4	178
missense		1	217	61	2	281
nonsense	8	5				13
start loss						0
frameshift	17	6	1			24
splice donor/acceptor (+/-2bp)	2	24	5	1		32
Total	27	36	226	233	6

Highest pathogenic variant AF is 0.00006478371

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CC2D1A	protein_coding	protein_coding	ENST00000318003	29	24679

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124739	0	66	124805	0.000264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.941	541	606	0.892	0.0000402	6060
Missense in Polyphen		172	199.42	0.86249		1987
Synonymous	0.212	247	251	0.983	0.0000170	1983
Loss of Function	4.99	15	55.0	0.273	0.00000286	615

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000216
Ashkenazi Jewish	0.00192	0.00169
East Asian	0.000446	0.000445
Finnish	0.00	0.00
European (Non-Finnish)	0.000196	0.000194
Middle Eastern	0.000446	0.000445
South Asian	0.000369	0.000360
Other	0.000508	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates the binding with FRE. May play a role in the altered regulation of HTR1A associated with anxiety and major depression. Mediates HDAC-independent repression of HTR1A promoter in neuronal cell. Performs essential function in controlling functional maturation of synapses (By similarity). Plays distinct roles depending on its localization. When cytoplasmic, acts as a scaffold protein in the PI3K/PDK1/AKT pathway. Repressor of HTR1A when nuclear. In the centrosome, regulates spindle pole localization of the cohesin subunit SCC1/RAD21, thereby mediating centriole cohesion during mitosis. {ECO:0000250, ECO:0000269|PubMed:20171170}.
• Disease: DISEASE: Mental retardation, autosomal recessive 3 (MRT3) [MIM:608443]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. {ECO:0000269|PubMed:16033914}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;EGFR1 (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.719
• rvis_EVS: 1.45
• rvis_percentile_EVS: 95.16

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

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

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of I-kappaB kinase/NF-kappaB signaling
• Cellular component: fibrillar center;nucleus;microtubule organizing center;cytosol;plasma membrane;membrane;extracellular exosome
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;protein binding;cadherin binding