CCDC88A

coiled-coil domain containing 88A

Basic information

Region (hg38): 2:55287841-55419895

Previous symbols: [ "KIAA1212" ]

Links

ENSG00000115355 ∙ NCBI:55704 ∙ OMIM:609736 ∙ HGNC:25523 ∙ Uniprot:Q3V6T2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PEHO-like syndrome (Limited), mode of inheritance: AR
• PEHO-like syndrome (Supportive), mode of inheritance: AR
• PEHO-like syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
PEHO-like syndrome	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	Craniofacial; Neurologic	26917597

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC88A gene.

• not provided (803 variants)
• Inborn genetic diseases (52 variants)
• PEHO-like syndrome (11 variants)
• PEHO syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC88A gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	216	12	235
missense			404	5	7	416
nonsense	5			1		6
start loss						0
frameshift	13					13
inframe indel			4			4
splice donor/acceptor (+/-2bp)		2		1		3
splice region			14	30	5	49
non coding			4	95	11	110
Total	18	2	419	318	30

Highest pathogenic variant AF is 0.00000658

Variants in CCDC88A

This is a list of pathogenic ClinVar variants found in the CCDC88A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-55291715-G-A			Uncertain significance (Aug 07, 2022)
2-55291717-G-A			Likely benign (Jan 19, 2021)
2-55291722-G-C			Uncertain significance (Jul 19, 2022)
2-55291726-C-T			Likely benign (Aug 17, 2023)
2-55291738-G-A			Likely benign (Jun 21, 2022)
2-55291744-T-A			Likely benign (Oct 28, 2023)
2-55291745-G-A			Uncertain significance (Mar 04, 2022)
2-55291746-A-C			Uncertain significance (Dec 14, 2020)
2-55291767-T-C		CCDC88A-related disorder	Benign (Jan 02, 2024)
2-55295587-T-C			Likely benign (Nov 10, 2023)
2-55295588-G-A			Likely benign (Sep 03, 2023)
2-55295589-G-GT			Likely benign (Nov 24, 2022)
2-55295598-A-G			Uncertain significance (Apr 23, 2021)
2-55295614-T-C			Uncertain significance (Sep 17, 2021)
2-55295649-T-A			Likely benign (Oct 21, 2021)
2-55295651-T-C			Uncertain significance (Nov 01, 2022)
2-55295651-T-G			Uncertain significance (Jul 23, 2022)
2-55295654-G-T		not specified	Uncertain significance (Dec 19, 2022)
2-55295662-C-T			Uncertain significance (Jul 06, 2022)
2-55295664-G-A			Likely benign (Jan 18, 2024)
2-55295671-G-T			Uncertain significance (Oct 20, 2021)
2-55295679-A-G			Likely benign (Jan 15, 2023)
2-55295687-T-C		not specified	Uncertain significance (Oct 13, 2023)
2-55295689-C-T			Uncertain significance (Sep 23, 2021)
2-55295691-T-C			Likely benign (Nov 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC88A	protein_coding	protein_coding	ENST00000336838	32	132080

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.94e-12	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	678	873	0.776	0.0000432	12365
Missense in Polyphen		220	335.94	0.65489		4999
Synonymous	-0.175	317	313	1.01	0.0000152	3279
Loss of Function	8.66	7	101	0.0695	0.00000558	1329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000679	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000470	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000329	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Enhances phosphoinositide 3-kinase (PI3K)- dependent phosphorylation and kinase activity of AKT1/PKB, but does not possess kinase activity itself (By similarity). Phosphorylation of AKT1/PKB thereby induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Essential for the integrity of the actin cytoskeleton and for cell migration (PubMed:16139227). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:27623382}.
• Disease: DISEASE: PEHO-like syndrome (PEHOL) [MIM:617507]: An autosomal recessive syndrome characterized by microcephaly and moderately severe hypotonia manifesting at birth, seizures that progress into infantile spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria and pachygyria, thin corpus callosum, and mild reduction in cerebellar vermis volume. Patients also display optic atrophy, severe cognitive delay, puffiness of the maxillary region of the face, and edema of the dorsum of the hands and feet. {ECO:0000269|PubMed:26917597}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mesodermal Commitment Pathway (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.487
• rvis_EVS: -1.57
• rvis_percentile_EVS: 3.19

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.704
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.840

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc88a
• Phenotype: growth/size/body region phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of protein phosphorylation;DNA replication;regulation of DNA replication;regulation of neuron projection development;cell migration;lamellipodium assembly;cytoskeleton-dependent intracellular transport;cytoplasmic microtubule organization;TOR signaling;activation of protein kinase B activity;regulation of actin cytoskeleton organization;regulation of cell population proliferation;positive regulation of cilium assembly;membrane organization;positive regulation of protein localization to cilium
• Cellular component: cytoplasm;endoplasmic reticulum;Golgi apparatus;centrosome;centriole;cytosol;plasma membrane;membrane;lamellipodium;cytoplasmic vesicle;ciliary basal body
• Molecular function: actin binding;microtubule binding;phosphatidylinositol binding;protein homodimerization activity;protein kinase B binding;dynein light intermediate chain binding