ANK1

ankyrin 1, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:41653219-41896741

Previous symbols: [ "ANK" ]

Links

ENSG00000029534 ∙ NCBI:286 ∙ OMIM:612641 ∙ HGNC:492 ∙ Uniprot:P16157 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spherocytosis type 1 (Strong), mode of inheritance: AD
• hereditary spherocytosis (Supportive), mode of inheritance: AD
• hereditary spherocytosis type 1 (Strong), mode of inheritance: AD
• hereditary spherocytosis type 1 (Limited), mode of inheritance: AR
• hereditary spherocytosis (Limited), mode of inheritance: AR
• hereditary spherocytosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spherocytosis, type 1	AD/AR	Hematologic	Some individuals may have therapy requiring neonatal hyperbilirubinemia, as well as severe, transfusion-requiring anemia	Hematologic	14467968; 4476391; 2675425; 1832935; 1486040; 8640229; 9887280; 9430667; 17327413; 20512576; 32436265

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANK1 gene.

• Hereditary spherocytosis type 1 (542 variants)
• not provided (458 variants)
• Spherocytosis (203 variants)
• Inborn genetic diseases (74 variants)
• not specified (37 variants)
• ANK1-related condition (22 variants)
• Spherocytosis, Dominant (12 variants)
• Spherocytosis, type 1, autosomal recessive (3 variants)
• Anemia (1 variants)
• Immunodeficiency 62 (1 variants)
• See cases (1 variants)
• Hemolytic anemia (1 variants)
• Hereditary spherocytosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANK1 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			30	76	11	117
missense	1	2	273	11	2	289
nonsense	44	31				75
start loss		1				1
frameshift	47	81	2			130
inframe indel			2			2
splice donor/acceptor (+/-2bp)	11	36	1			48
splice region			14	7	1	22
non coding	1	2	64	24	85	176
Total	104	153	372	111	98

Highest pathogenic variant AF is 0.0000197

Variants in ANK1

This is a list of pathogenic ClinVar variants found in the ANK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-41653381-G-A		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 13, 2018)
8-41653448-G-C		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41653509-G-A		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41653518-G-C			Uncertain significance (Jan 15, 2021)
8-41653618-G-T		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 12, 2018)
8-41653638-A-C		Hereditary spherocytosis type 1 • Spherocytosis	Benign (Jan 13, 2018)
8-41653667-C-A		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 12, 2018)
8-41653768-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Benign/Likely benign (Jan 13, 2018)
8-41653838-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 12, 2018)
8-41653891-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Benign/Likely benign (Jan 12, 2018)
8-41653898-C-A		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41653898-C-T		Spherocytosis • Hereditary spherocytosis type 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
8-41653906-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41653910-G-T		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41653932-T-G		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41653982-T-C		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41654082-C-G		Hereditary spherocytosis type 1 • Spherocytosis	Conflicting classifications of pathogenicity (Apr 01, 2023)
8-41654123-A-T		Hereditary spherocytosis type 1	Likely benign (Apr 27, 2017)
8-41654181-G-C		Hereditary spherocytosis type 1 • Spherocytosis	Benign/Likely benign (Jan 13, 2018)
8-41654187-G-C		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41654200-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41654316-G-A		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41654366-G-A		Spherocytosis • Hereditary spherocytosis type 1	Uncertain significance (Jan 12, 2018)
8-41654378-C-T		Hereditary spherocytosis type 1 • Spherocytosis	Uncertain significance (Jan 13, 2018)
8-41654388-C-A		Hereditary spherocytosis type 1 • Spherocytosis	Conflicting classifications of pathogenicity (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANK1	protein_coding	protein_coding	ENST00000265709	43	243542

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.23e-9	125584	0	164	125748	0.000652

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.08	927	1.12e+3	0.825	0.0000764	12316
Missense in Polyphen		354	506.3	0.69919		5445
Synonymous	-0.648	502	484	1.04	0.0000361	3884
Loss of Function	8.06	9	92.8	0.0970	0.00000505	1064

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00307	0.00298
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000438	0.000435
Finnish	0.00121	0.00120
European (Non-Finnish)	0.000612	0.000607
Middle Eastern	0.000438	0.000435
South Asian	0.00	0.00
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. {ECO:0000269|PubMed:12456646}.
• Disease: DISEASE: Spherocytosis 1 (SPH1) [MIM:182900]: A form of spherocytosis, a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH1 is characterized by severe hemolytic anemia. Inheritance can be autosomal dominant or autosomal recessive. Patients with homozygous mutations have a more severe disorder. {ECO:0000269|PubMed:11102985, ECO:0000269|PubMed:8640229}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);Developmental Biology;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;NrCAM interactions;CHL1 interactions;Neurofascin interactions;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Interaction between L1 and Ankyrins;L1CAM interactions;COPI-mediated anterograde transport;Axon guidance;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.748

Intolerance Scores

• loftool: 0.109
• rvis_EVS: -3.14
• rvis_percentile_EVS: 0.45

Haploinsufficiency Scores

• pHI: 0.753
• hipred: Y
• hipred_score: 0.825
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ank1
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); hematopoietic system phenotype; 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); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: exocytosis;endoplasmic reticulum to Golgi vesicle-mediated transport;cytoskeleton organization;signal transduction;positive regulation of organelle organization;maintenance of epithelial cell apical/basal polarity;protein localization to plasma membrane
• Cellular component: nucleus;cytosol;cytoskeleton;plasma membrane;cytoplasmic side of plasma membrane;spectrin-associated cytoskeleton;membrane;basolateral plasma membrane;sarcoplasmic reticulum;Z disc;axolemma;M band;sarcolemma;axon initial segment;postsynaptic membrane
• Molecular function: structural molecule activity;structural constituent of cytoskeleton;protein binding;cytoskeletal adaptor activity;enzyme binding;protein phosphatase binding;spectrin binding;ion channel binding;ATPase binding