KANK2

KN motif and ankyrin repeat domains 2, the group of KN motif and ankyrin repeat domain containing

Basic information

Region (hg38): 19:11164270-11197791

Previous symbols: [ "MXRA3", "ANKRD25" ]

Links

ENSG00000197256 ∙ NCBI:25959 ∙ OMIM:614610 ∙ HGNC:29300 ∙ Uniprot:Q63ZY3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• wooly hair-palmoplantar keratoderma syndrome (Supportive), mode of inheritance: AR
• wooly hair-palmoplantar keratoderma syndrome (Limited), mode of inheritance: Unknown
• nephrotic syndrome 16 (Limited), mode of inheritance: Unknown
• wooly hair-palmoplantar keratoderma syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome 16; Palmoplantar keratoderma and woolly hair	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	Dermatologic; Musculoskeletal; Renal	11874502; 24671081; 25961457

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KANK2 gene.

• not_provided (337 variants)
• not_specified (151 variants)
• KANK2-related_disorder (34 variants)
• Nephrotic_syndrome_16 (12 variants)
• Wooly_hair-palmoplantar_keratoderma_syndrome (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KANK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001136191.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	96	7	107
missense	2		244	31	4	281
nonsense			1			1
start loss			1			1
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	2	0	252	127	11

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KANK2	protein_coding	protein_coding	ENST00000432929	11	33525

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0450	0.955	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.484	549	582	0.944	0.0000413	5423
Missense in Polyphen		299	326.22	0.91656		2949
Synonymous	-1.25	284	258	1.10	0.0000193	1890
Loss of Function	3.88	9	33.1	0.272	0.00000182	337

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000221	0.000217
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.00427	0.00387
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000216	0.000211
Middle Eastern	0.00427	0.00387
South Asian	0.0000328	0.0000327
Other	0.000177	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcription regulation by sequestering nuclear receptor coactivators, such as NCOA1, NCOA2 and NCOA3, in the cytoplasm; the function is deregulated by phosphorylation. Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). May be involved in the control of cytoskeleton formation by regulating actin polymerization. Involved in regulation of caspase-independent apoptosis; proposed to sequester AIFM1 in mitochondria and apoptotic stimuli lead to its proteasomal degradation allowing the release of AIFM1 to the nucleus (PubMed:22371500). May be involved in promotion of cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q8BX02, ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:24671081}.
• Disease: DISEASE: Palmoplantar keratoderma and woolly hair (PPKWH) [MIM:616099]: A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. {ECO:0000269|PubMed:24671081}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.357
• rvis_EVS: 0.59
• rvis_percentile_EVS: 82.38

Haploinsufficiency Scores

• pHI: 0.331
• hipred: N
• hipred_score: 0.485
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.237

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kank2

Zebrafish Information Network

• Gene name: kank2
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;apoptotic process;negative regulation of cell population proliferation;negative regulation of intracellular estrogen receptor signaling pathway;regulation of Rho protein signal transduction;negative regulation of programmed cell death;negative regulation of vitamin D receptor signaling pathway;kidney epithelium development;glomerular visceral epithelial cell migration;negative regulation of G1/S transition of mitotic cell cycle
• Cellular component: cytoplasm;mitochondrion
• Molecular function: protein binding