CUL7

cullin 7, the group of Cullins

Basic information

Region (hg38): 6:43037616-43053943

Previous symbols: [ "KIAA0076" ]

Links

ENSG00000044090 ∙ NCBI:9820 ∙ OMIM:609577 ∙ HGNC:21024 ∙ Uniprot:Q14999 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3M syndrome 1 (Definitive), mode of inheritance: AR
• 3M syndrome 1 (Definitive), mode of inheritance: AR
• 3-M syndrome (Supportive), mode of inheritance: AR
• 3M syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Three M syndrome 1	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; Musculoskeletal	16142236; 17675530; 19225462; 21166787; 22624670; 22974575

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CUL7 gene.

• not provided (516 variants)
• 3M syndrome 1 (170 variants)
• Inborn genetic diseases (65 variants)
• not specified (32 variants)
• 3-M syndrome (9 variants)
• CUL7-related condition (3 variants)
• - (1 variants)
• Growth delay;Short stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CUL7 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			29	80	14	123
missense	1	4	272	10	12	299
nonsense	26	2	2			30
start loss						0
frameshift	22	7	3			32
inframe indel		1	3	1		5
splice donor/acceptor (+/-2bp)	2	7				9
splice region			12	12	1	25
non coding			12	38	24	74
Total	51	21	321	129	50

Highest pathogenic variant AF is 0.0000853

Variants in CUL7

This is a list of pathogenic ClinVar variants found in the CUL7 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-43037617-T-C		3M syndrome 1	Uncertain significance (Jan 12, 2018)
6-43037631-T-C		3M syndrome 1	Uncertain significance (Jan 13, 2018)
6-43037692-C-A			Uncertain significance (Oct 24, 2022)
6-43037692-C-T		3M syndrome 1	Uncertain significance (Jul 10, 2023)
6-43037697-G-A		not specified • 3M syndrome 1	Benign (Jan 25, 2024)
6-43037705-A-C		Inborn genetic diseases	Uncertain significance (Feb 21, 2022)
6-43037713-G-A		3M syndrome 1	Uncertain significance (Dec 21, 2022)
6-43037744-G-A		3M syndrome 1	Uncertain significance (Apr 24, 2022)
6-43037744-G-C		3M syndrome 1	Uncertain significance (Aug 26, 2019)
6-43037754-CTG-C		3M syndrome 1	Uncertain significance (Sep 13, 2019)
6-43037756-G-A		not specified	Uncertain significance (Dec 21, 2022)
6-43037756-G-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
6-43037774-G-A			Uncertain significance (Aug 12, 2021)
6-43037774-G-T			Uncertain significance (Jan 06, 2023)
6-43037813-C-T		3M syndrome 1	Uncertain significance (Jan 12, 2018)
6-43037830-A-G			Uncertain significance (Nov 27, 2023)
6-43037834-T-G		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
6-43037848-T-C			Uncertain significance (Feb 10, 2021)
6-43037849-A-G			Uncertain significance (Aug 25, 2017)
6-43037850-G-A		3M syndrome 1	Benign/Likely benign (Feb 01, 2024)
6-43037866-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
6-43037868-G-A		CUL7-related disorder	Likely benign (Apr 01, 2022)
6-43037871-G-A		not specified	Benign/Likely benign (Oct 06, 2023)
6-43037873-C-CA		-	no classification for the single variant (-)
6-43037878-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CUL7	protein_coding	protein_coding	ENST00000535468	26	16329

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.59e-21	1.00	125647	0	101	125748	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.543	959	1.01e+3	0.952	0.0000653	11513
Missense in Polyphen		310	339.81	0.91228		3945
Synonymous	-0.212	430	424	1.01	0.0000266	3706
Loss of Function	3.59	47	82.0	0.573	0.00000460	878

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00157	0.00156
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000652	0.000653
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000223	0.000220
Middle Eastern	0.000652	0.000653
South Asian	0.000728	0.000719
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the 3M and Cul7-RING(FBXW8) complexes, which mediates the ubiquitination of target proteins. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695). Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5 (PubMed:24793696). Core component of a Cul7-RING ubiquitin-protein ligase with FBXW8, which mediates ubiquitination and consequent degradation of target proteins such as GORASP1, IRS1 and MAP4K1/HPK1 (PubMed:21572988, PubMed:24362026). Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain (PubMed:21572988). Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) (PubMed:18498745). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation (PubMed:24362026). Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development (PubMed:20139075). Does not promote polyubiquitination and proteasomal degradation of p53/TP53 (PubMed:16547496, PubMed:17332328). While the Cul7-RING(FBXW8) and the 3M complexes are associated and involved in common processes, CUL7 and the Cul7-RING(FBXW8) complex may be have additional functions. {ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:20139075, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
• Disease: DISEASE: 3M syndrome 1 (3M1) [MIM:273750]: An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies. {ECO:0000269|PubMed:16142236, ECO:0000269|PubMed:17675530, ECO:0000269|PubMed:23018678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);XBP1(S) activates chaperone genes;Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.253
• rvis_EVS: -1.53
• rvis_percentile_EVS: 3.39

Haploinsufficiency Scores

• pHI: 0.166
• hipred: Y
• hipred_score: 0.711
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.754

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cul7
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; 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); 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); respiratory system phenotype; embryo phenotype; skeleton phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;mitotic cytokinesis;vasculogenesis;epithelial to mesenchymal transition;placenta development;proteolysis;ubiquitin-dependent protein catabolic process;Golgi organization;regulation of mitotic nuclear division;viral process;protein ubiquitination;IRE1-mediated unfolded protein response;post-translational protein modification;positive regulation of dendrite morphogenesis
• Cellular component: anaphase-promoting complex;cytoplasm;Golgi apparatus;centrosome;cytosol;Cul7-RING ubiquitin ligase complex;perinuclear region of cytoplasm;3M complex
• Molecular function: protein binding;ubiquitin protein ligase binding