ANKS6

ankyrin repeat and sterile alpha motif domain containing 6, the group of Ankyrin repeat domain containing|Sterile alpha motif domain containing

Basic information

Region (hg38): 9:98731329-98796965

Previous symbols: [ "SAMD6", "ANKRD14" ]

Links

ENSG00000165138 ∙ NCBI:203286 ∙ OMIM:615370 ∙ HGNC:26724 ∙ Uniprot:Q68DC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis 2 (Supportive), mode of inheritance: AR
• nephronophthisis 1 (Supportive), mode of inheritance: AR
• nephronophthisis 16 (Strong), mode of inheritance: AR
• nephronophthisis 16 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis 16	AR	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Gastrointestinal; Renal	23793029
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANKS6 gene.

• Nephronophthisis 16 (14 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANKS6 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			1	96	4	101
missense		3	138	9	5	155
nonsense	5					5
start loss						0
frameshift	9	1	1			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	5	7		13
non coding				52	25	77
Total	15	6	142	157	34

Highest pathogenic variant AF is 0.000230

Variants in ANKS6

This is a list of pathogenic ClinVar variants found in the ANKS6 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-98736257-T-A			Likely benign (Jan 25, 2019)
9-98736282-C-G			Benign (Nov 10, 2018)
9-98736320-G-A			Likely benign (May 19, 2021)
9-98736327-T-C			Benign (May 10, 2020)
9-98736479-G-A			Benign (Sep 02, 2020)
9-98736502-G-T		not specified	Likely benign (-)
9-98736520-C-T		Nephronophthisis 16	Likely benign (Oct 25, 2021)
9-98736522-C-T		not specified • Nephronophthisis 16	Benign/Likely benign (Feb 06, 2023)
9-98736523-G-A		Nephronophthisis 16	Uncertain significance (Aug 19, 2021)
9-98736542-G-A		Nephronophthisis 16	Conflicting classifications of pathogenicity (Dec 06, 2023)
9-98736557-T-C		Nephronophthisis 16 • Inborn genetic diseases	Uncertain significance (May 24, 2023)
9-98736571-A-G		Nephronophthisis 16 • ANKS6-related disorder	Conflicting classifications of pathogenicity (Jan 24, 2024)
9-98736601-T-G		Nephronophthisis 16	Uncertain significance (May 27, 2022)
9-98736619-C-T		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
9-98736625-T-G		Nephronophthisis 16	Pathogenic (Aug 01, 2013)
9-98745307-G-A			Likely benign (May 10, 2020)
9-98745398-AC-A			Likely benign (Apr 09, 2021)
9-98745553-C-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
9-98745556-T-C		Nephronophthisis 16	Uncertain significance (Sep 27, 2022)
9-98745567-C-T		Nephronophthisis 16	Uncertain significance (Dec 11, 2018)
9-98745568-G-A		Nephronophthisis 16	Likely benign (Sep 20, 2023)
9-98745572-A-C		Nephronophthisis 16	Uncertain significance (Sep 01, 2021)
9-98745583-C-T		Nephronophthisis 16	Likely benign (Oct 15, 2021)
9-98745597-G-A			Uncertain significance (Sep 16, 2018)
9-98745629-TC-T		Nephronophthisis 16	Uncertain significance (Apr 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANKS6	protein_coding	protein_coding	ENST00000353234	15	65637

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000694	0.999	124731	0	66	124797	0.000264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0756	463	458	1.01	0.0000279	5561
Missense in Polyphen		130	147.33	0.88238		1742
Synonymous	0.121	199	201	0.989	0.0000139	1865
Loss of Function	2.89	14	31.5	0.444	0.00000168	380

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000356	0.000356
Ashkenazi Jewish	0.0000998	0.0000993
East Asian	0.000115	0.000111
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000279	0.000274
Middle Eastern	0.000115	0.000111
South Asian	0.000643	0.000588
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for renal function. {ECO:0000269|PubMed:23793029}.
• Disease: DISEASE: Nephronophthisis 16 (NPHP16) [MIM:615382]: A form of nephronophthisis, a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. Some patients have cystic kidneys of normal size and no extrarenal manifestations, whereas others have enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis. {ECO:0000269|PubMed:23793029}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.678
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.59

Haploinsufficiency Scores

• pHI: 0.134
• hipred: N
• hipred_score: 0.368
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.339

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Anks6
• Phenotype: growth/size/body region phenotype; embryo 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); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Cellular component: cytoplasm;cilium
• Molecular function: protein binding