ANKH

ANKH inorganic pyrophosphate transport regulator, the group of MicroRNA protein coding host genes|Solute carrier family 62

Basic information

Region (hg38): 5:14704800-14871778

Previous symbols: [ "CCAL2", "CMDJ" ]

Links

ENSG00000154122 ∙ NCBI:56172 ∙ OMIM:605145 ∙ HGNC:15492 ∙ Uniprot:Q9HCJ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• skeletal dysplasia (Moderate), mode of inheritance: AD
• chondrocalcinosis 2 (Strong), mode of inheritance: AD
• craniometaphyseal dysplasia, autosomal dominant (Strong), mode of inheritance: AD
• chondrocalcinosis 2 (Strong), mode of inheritance: AD
• craniometaphyseal dysplasia, autosomal dominant (Strong), mode of inheritance: AD
• chondrocalcinosis 2 (Supportive), mode of inheritance: AD
• craniometaphyseal dysplasia (Supportive), mode of inheritance: AD
• craniometaphyseal dysplasia, autosomal dominant (Definitive), mode of inheritance: AD
• chondrocalcinosis 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniometaphyseal dysplasia, autosomal dominant; Chondrocalcinosis 2	AD	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	Craniofacial; Musculoskeletal	8528213; 9915952; 11326272; 11326338; 12297987; 12297989; 20301634; 20358596; 22150416; 22647861

ClinVar

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

• not_provided (281 variants)
• Craniometaphyseal_dysplasia,_autosomal_dominant (52 variants)
• Chondrocalcinosis_2 (46 variants)
• Inborn_genetic_diseases (46 variants)
• ANKH-related_disorder (15 variants)
• not_specified (6 variants)
• Intellectual_disability (2 variants)
• Rare_epilepsy (1 variants)
• Benign_familial_infantile_epilepsy (1 variants)
• CHONDROCALCINOSIS_2,_SPORADIC (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANKH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000054027.6. 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			3	72	6	81
missense	4	4	121	12		141
nonsense			1			1
start loss						0
frameshift	1		2			3
splice donor/acceptor (+/-2bp)		1	4			5
Total	5	5	131	84	6

Highest pathogenic variant AF is 0.000027364424

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANKH	protein_coding	protein_coding	ENST00000284268	12	166978

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	184	298	0.617	0.0000188	3220
Missense in Polyphen		38	124.85	0.30435		1349
Synonymous	-1.21	141	124	1.14	0.00000902	995
Loss of Function	3.24	5	21.1	0.237	9.11e-7	263

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000476	0.0000462
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
• Disease: DISEASE: Craniometaphyseal dysplasia, autosomal dominant (CMDD) [MIM:123000]: An osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy. {ECO:0000269|PubMed:11326272, ECO:0000269|PubMed:11326338}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: regulators of bone mineralization;Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Intolerance Scores

• loftool: 0.115
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.405

Gene Damage Prediction

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

Gene ontology

• Biological process: skeletal system development;locomotory behavior;regulation of bone mineralization;inorganic diphosphate transport;phosphate ion transmembrane transport;transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;outer membrane
• Molecular function: inorganic phosphate transmembrane transporter activity;phosphate ion transmembrane transporter activity;inorganic diphosphate transmembrane transporter activity