KLHDC8B

kelch domain containing 8B

Basic information

Region (hg38): 3:49171597-49176486

Links

ENSG00000185909 ∙ NCBI:200942 ∙ OMIM:613169 ∙ HGNC:28557 ∙ Uniprot:Q8IXV7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• classic Hodgkin lymphoma (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hodgkin lymphoma, classic	AD	Oncologic	Surveillance and/or awareness of cancer risk may allow early diagnosis, which could potentially be beneficial	Oncologic	19706467
One family with a gene disruption has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHDC8B gene.

• not provided (33 variants)
• Inborn genetic diseases (15 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHDC8B 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				12	2	14
missense			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1	1	3
non coding			1	5		6
Total	0	0	25	18	2

Variants in KLHDC8B

This is a list of pathogenic ClinVar variants found in the KLHDC8B region.

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

Position	Type	Phenotype	Significance	ClinVar
3-49171662-C-T		Classic Hodgkin lymphoma	Pathogenic (Sep 01, 2009)
3-49172761-G-T		not specified	Uncertain significance (Nov 09, 2017)
3-49172788-C-T		not specified	Uncertain significance (Dec 26, 2023)
3-49172811-C-T			Likely benign (Sep 21, 2022)
3-49172830-C-T		not specified	Uncertain significance (Apr 20, 2023)
3-49172837-A-G			Uncertain significance (Jan 29, 2024)
3-49172891-G-A			Uncertain significance (Sep 25, 2022)
3-49172903-C-T			Uncertain significance (Dec 04, 2022)
3-49172933-C-T		not specified	Uncertain significance (Aug 08, 2022)
3-49172936-C-T			Uncertain significance (Feb 21, 2023)
3-49172938-C-T		not specified	Uncertain significance (Oct 13, 2023)
3-49172940-C-T			Likely benign (Sep 15, 2023)
3-49172953-C-T			Likely benign (Aug 21, 2022)
3-49172969-C-T		not specified	Uncertain significance (Jan 22, 2024)
3-49172975-G-A		not specified	Uncertain significance (Apr 08, 2022)
3-49172991-G-A		KLHDC8B-related disorder	Likely benign (Oct 09, 2020)
3-49172991-G-T			Likely benign (Aug 29, 2023)
3-49173019-G-T			Uncertain significance (Mar 17, 2023)
3-49173048-G-A			Benign (Sep 30, 2023)
3-49173073-A-T			Uncertain significance (Nov 19, 2022)
3-49173081-G-A			Likely benign (Aug 04, 2023)
3-49173085-C-T			Uncertain significance (Dec 12, 2023)
3-49173094-C-T			Uncertain significance (Apr 07, 2023)
3-49173095-G-A		not specified	Uncertain significance (Oct 20, 2023)
3-49173131-C-T		not specified	Uncertain significance (Mar 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHDC8B	protein_coding	protein_coding	ENST00000332780	5	4874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00179	0.907	125729	0	13	125742	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	165	234	0.706	0.0000146	2246
Missense in Polyphen		63	99.015	0.63627		947
Synonymous	0.509	81	87.0	0.931	0.00000453	809
Loss of Function	1.47	6	11.4	0.528	4.87e-7	125

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000453	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pinching off the separated nuclei at the cleavage furrow and in cytokinesis (PubMed:20107318). Required for mitotic integrity and maintenance of chromosomal stability. Protects cells against mitotic errors, centrosomal amplification, micronucleus formation and aneuploidy. Plays a key role of midbody function involving abscission of the daughter cells during cytokinesis and appropriate chromosomal and nuclear segregation into the daughter cells (PubMed:22988245, PubMed:23713010). {ECO:0000269|PubMed:20107318, ECO:0000269|PubMed:22988245, ECO:0000269|PubMed:23713010}.
• Disease: DISEASE: Lymphoma, Hodgkin, classic (CHL) [MIM:236000]: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen and general lymphoid tissue, and the presence of large, usually multinucleate, cells (Reed-Sternberg cells). Reed-Sternberg cells compose only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils and histiocytes. {ECO:0000269|PubMed:19706467}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A variant in the 5'-UTR of KLHDC8B, responsible for decreasing its expression, is associated with classic Hodgkin lymphoma and segregates with the disease in some families (PubMed:19706467). {ECO:0000269|PubMed:19706467}.; DISEASE: Note=A chromosomal aberration disrupting KLHDC8B has been found in a family with the nodular sclerosis type of Hodgkin lymphoma. Translocation t(2,3)(q11.2;p21.31).

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.299
• hipred: Y
• hipred_score: 0.546
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.216

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhdc8b

Gene ontology

• Biological process: nuclear chromosome segregation;mitotic nuclear division;mitotic cytokinetic process
• Cellular component: cytoplasm;cytosol;midbody;intercellular bridge;cellularization cleavage furrow