CLTC

clathrin heavy chain, the group of Clathrin subunits

Basic information

Region (hg38): 17:59619680-59696956

Previous symbols: [ "CLTCL2" ]

Links

ENSG00000141367

∙ NCBI:1213 ∙ OMIM:118955 ∙ HGNC:2092 ∙ Uniprot:Q00610 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 56	AD	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; Musculoskeletal; Neurologic	26822784; 29100083; 31961069

ClinVar

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

not_provided (936 variants)
Intellectual_disability,_autosomal_dominant_56 (93 variants)
Inborn_genetic_diseases (62 variants)
CLTC-related_disorder (30 variants)
not_specified (12 variants)
Intellectual_disability (3 variants)
Global_developmental_delay (2 variants)
Neurodevelopmental_disorder (1 variants)
Abnormal_corpus_callosum_morphology (1 variants)
See_cases (1 variants)
Noonan_syndrome_3 (1 variants)
Autosomal_dominant_non-syndromic_intellectual_disability (1 variants)
Neurodevelopmental_abnormality (1 variants)
Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLTC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004859.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		13 clinvar	249 clinvar	11 clinvar	274
missense	5 clinvar	11 clinvar	390 clinvar	9 clinvar		415
nonsense	20 clinvar	9 clinvar	2 clinvar			31
start loss						0
frameshift	28 clinvar	22 clinvar	1 clinvar			51
splice donor/acceptor (+/-2bp)	3 clinvar	10 clinvar	3 clinvar	1 clinvar		17
Total	57	52	409	259	11

Highest pathogenic variant AF is 0.000009914

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLTC	protein_coding	protein_coding	ENST00000269122	32	76453

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.09e-12	125714	0	26	125740	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	7.76	251	910	0.276	0.0000487	11088
Missense in Polyphen		61	376.62	0.16197		4984
Synonymous	1.63	276	313	0.882	0.0000159	3142
Loss of Function	8.31	4	88.2	0.0453	0.00000457	1059

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000475	0.000475
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000799	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000364	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as component of the TACC3/ch- TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter- microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). {ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}.;
Disease: DISEASE: Mental retardation, autosomal dominant 56 (MRD56) [MIM:617854]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26822784, ECO:0000269|PubMed:29100083}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Synaptic vesicle cycle - Homo sapiens (human);Endocytosis - Homo sapiens (human);Lysosome - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Synaptic Vesicle Pathway;VEGFA-VEGFR2 Signaling Pathway;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Developmental Biology;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Signaling by WNT;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;Membrane Trafficking;Entry of Influenza Virion into Host Cell via Endocytosis;Influenza Life Cycle;Influenza Infection;MHC class II antigen presentation;TCR;Infectious disease;Immune System;LDL clearance;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Adaptive Immune System;Retrograde neurotrophin signalling;Transport of small molecules;CRH;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);WNT5A-dependent internalization of FZD4;PCP/CE pathway;Signaling by NTRKs;EGFR1;Beta-catenin independent WNT signaling;Plasma lipoprotein assembly, remodeling, and clearance;Cargo recognition for clathrin-mediated endocytosis;Arf6 trafficking events;L1CAM interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;FAS (CD95) signaling pathway (Consensus)

Recessive Scores

pRec: 0.946

Intolerance Scores

loftool: 0.190
rvis_EVS: -1.31
rvis_percentile_EVS: 4.85

Haploinsufficiency Scores

pHI: 0.647
hipred: Y
hipred_score: 0.729
ghis: 0.661

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cltc
Phenotype

Zebrafish Information Network

Gene name: cltca
Affected structure: caudal vein plexus
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: mitotic cell cycle;osteoblast differentiation;intracellular protein transport;receptor-mediated endocytosis;autophagy;antigen processing and presentation of exogenous peptide antigen via MHC class II;receptor internalization;low-density lipoprotein particle receptor catabolic process;transferrin transport;low-density lipoprotein particle clearance;retrograde transport, endosome to Golgi;transcytosis;clathrin coat assembly;cell division;Wnt signaling pathway, planar cell polarity pathway;regulation of mitotic spindle organization;membrane organization;clathrin-dependent endocytosis;negative regulation of hyaluronan biosynthetic process;negative regulation of protein localization to plasma membrane
Cellular component: lysosome;endosome;spindle;cytosol;plasma membrane;focal adhesion;membrane;clathrin coat;clathrin coat of trans-Golgi network vesicle;clathrin coat of coated pit;clathrin-coated vesicle;clathrin-coated endocytic vesicle membrane;trans-Golgi network membrane;protein-containing complex;endolysosome membrane;melanosome;intracellular membrane-bounded organelle;clathrin-coated endocytic vesicle;extracellular exosome;clathrin complex;mitotic spindle;extracellular vesicle;mitotic spindle microtubule
Molecular function: RNA binding;double-stranded RNA binding;structural molecule activity;protein binding;protein kinase binding;clathrin light chain binding;low-density lipoprotein particle receptor binding;disordered domain specific binding;ubiquitin-specific protease binding