KLLN

killin, p53 regulated DNA replication inhibitor

Basic information

Region (hg38): 10:87859157-87863533

Links

ENSG00000227268 ∙ NCBI:100144748 ∙ OMIM:612105 ∙ HGNC:37212 ∙ Uniprot:B2CW77 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cowden syndrome 4 (No Known Disease Relationship), mode of inheritance: Unknown
• Cowden disease (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cowden syndrome 4	AD	Oncologic	Individuals have been reported with a high risk of breast and renal cancer, and surveillance may allow early diagnosis and management of neoplastic processes	Dermatologic; Oncologic	21177507; 21956414
Germline hypermethylation and epigenetic inactivation of the KLLN promoter has been described in affected individuals

ClinVar

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

• Hereditary cancer-predisposing syndrome (146 variants)
• not provided (143 variants)
• not specified (58 variants)
• PTEN hamartoma tumor syndrome (16 variants)
• Inborn genetic diseases (13 variants)
• Cowden syndrome 1 (5 variants)
• Cowden syndrome 4 (5 variants)
• 7 conditions (3 variants)
• Macrocephaly-autism syndrome;Familial meningioma;Malignant tumor of prostate;Cowden syndrome 1;Glioma susceptibility 2 (2 variants)
• PTEN-related condition (2 variants)
• Familial meningioma;Malignant tumor of prostate;Glioma susceptibility 2;Macrocephaly-autism syndrome;Cowden syndrome 1 (1 variants)
• Seizure (1 variants)
• Macrocephaly-autism syndrome;Glioma susceptibility 2;Familial meningioma;Malignant tumor of prostate;Cowden syndrome 1 (1 variants)
• Malignant tumor of prostate;Macrocephaly-autism syndrome;Familial meningioma;Glioma susceptibility 2;Cowden syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLLN 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			4	2		6
missense			22	2	4	28
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			239	10	6	255
Total	0	0	266	14	10

Variants in KLLN

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

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

Position	Type	Phenotype	Significance	ClinVar
10-87861962-G-T		Cowden syndrome 4	Uncertain significance (May 24, 2021)
10-87861970-T-C		not specified	Uncertain significance (Jul 23, 2019)
10-87861989-G-A		not specified	Likely benign (Jan 29, 2024)
10-87862000-T-A		not specified	Uncertain significance (Feb 16, 2023)
10-87862028-G-A		not specified	Uncertain significance (Mar 01, 2023)
10-87862043-A-T		not specified	Benign (Nov 01, 2023)
10-87862046-A-G		not specified	Likely benign (Nov 27, 2023)
10-87862057-C-T		not specified	Uncertain significance (Nov 08, 2022)
10-87862096-T-C		not specified	Benign (Nov 01, 2023)
10-87862104-G-A		not specified	Uncertain significance (Mar 03, 2020)
10-87862106-G-C		not specified • KLLN-related disorder	Benign (Nov 01, 2023)
10-87862120-C-T		not specified	Uncertain significance (Dec 03, 2021)
10-87862144-GCC-G		not specified	Uncertain significance (Apr 20, 2020)
10-87862147-CCT-C		not specified • KLLN-related disorder	Conflicting classifications of pathogenicity (Aug 15, 2023)
10-87862172-G-T		PTEN hamartoma tumor syndrome	Uncertain significance (May 28, 2019)
10-87862192-C-T		not specified	Uncertain significance (Oct 05, 2021)
10-87862193-A-AACC		KLLN-related disorder	Likely benign (Apr 06, 2022)
10-87862249-C-T		not specified	Uncertain significance (Feb 05, 2024)
10-87862253-G-T		not specified	Uncertain significance (Apr 20, 2020)
10-87862254-G-T		not specified	Uncertain significance (Apr 20, 2020)
10-87862262-A-G		Cowden syndrome 4	Uncertain significance (May 24, 2021)
10-87862282-A-G		not specified	Uncertain significance (Jan 23, 2024)
10-87862284-G-A		not specified	Uncertain significance (Nov 30, 2021)
10-87862297-C-T		not specified	Uncertain significance (Apr 04, 2023)
10-87862304-G-C		Cowden syndrome 4	Uncertain significance (Apr 15, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLLN	protein_coding	protein_coding	ENST00000445946	1	4277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00505	0.477	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.967	116	90.2	1.29	0.00000408	1109
Missense in Polyphen		38	26.776	1.4192		342
Synonymous	-2.09	55	38.5	1.43	0.00000176	403
Loss of Function	-0.219	3	2.62	1.15	1.12e-7	23

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating p53/TP53-induced apoptosis. Has the ability to inhibit DNA synthesis and S phase arrest coupled to apoptosis. Has affinity to both double- and single- stranded DNA. {ECO:0000269|PubMed:18385383}.
• Disease: DISEASE: Cowden syndrome 4 (CWS4) [MIM:615107]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:21177507}. Note=The gene represented in this entry is involved in disease pathogenesis. Germline KLLN methylation is common among patients with Cowden syndrome or Cowden-like syndrome and is associated with increased risks of breast and renal cancer over PTEN mutation-positive individuals (PubMed:21177507). {ECO:0000269|PubMed:21177507}.

Intolerance Scores

• rvis_EVS: 1.01
• rvis_percentile_EVS: 90.83

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Gene ontology

• Biological process: apoptotic process;cell cycle arrest
• Cellular component: nucleus;nucleolus
• Molecular function: DNA binding