HYCC1

hyccin PI4KA lipid kinase complex subunit 1, the group of PI4KA lipid kinase complex

Basic information

Region (hg38): 7:22889371-23014130

Previous symbols: [ "FAM126A" ]

Links

ENSG00000122591 ∙ NCBI:84668 ∙ OMIM:610531 ∙ HGNC:24587 ∙ Uniprot:Q9BYI3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 5 (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 5 (Definitive), mode of inheritance: AR
• hypomyelinating leukodystrophy 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 5	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	Neurologic; Ophthalmologic	16951682

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HYCC1 gene.

• Hypomyelination_and_Congenital_Cataract (201 variants)
• Inborn_genetic_diseases (64 variants)
• not_provided (41 variants)
• HYCC1-related_disorder (18 variants)
• not_specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HYCC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032581.4. 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	62	3	69
missense	1	1	114	13	1	130
nonsense	1	5	2			8
start loss						0
frameshift	1	4				5
splice donor/acceptor (+/-2bp)	3	4	2			9
Total	6	14	122	75	4

Highest pathogenic variant AF is 0.0000504862

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HYCC1	protein_coding	protein_coding	ENST00000432176	10	72872

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.121	0.879	125724	0	22	125746	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.981	224	269	0.832	0.0000131	3374
Missense in Polyphen		59	95.813	0.61578		1226
Synonymous	-1.41	117	99.2	1.18	0.00000518	1001
Loss of Function	3.58	7	27.1	0.258	0.00000136	351

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:26571211). FAM126A plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P (PubMed:26571211). Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system (PubMed:26571211, PubMed:16951682). May also have a role in the beta-catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 5 (HLD5) [MIM:610532]: A hypomyelinating leukodystrophy associated with congenital cataract. It is clinically characterized by congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency. Affected individuals experience progressive pyramidal and cerebellar dysfunction, muscle weakness and wasting prevailingly in the lower limbs. Mental deficiency ranges from mild to moderate. HLD5 shows clinical variability, but features of hypomyelination combined with increased periventricular white matter water content are consistently observed. {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:21911699, ECO:0000269|PubMed:23998934, ECO:0000269|PubMed:26571211}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.170

Intolerance Scores

• loftool: 0.507
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.52

Haploinsufficiency Scores

• pHI: 0.227
• hipred: Y
• hipred_score: 0.595
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.486

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fam126a
• Phenotype: normal phenotype

Gene ontology

• Biological process: myelination;phosphatidylinositol phosphorylation;protein localization to plasma membrane
• Cellular component: cytosol;plasma membrane;neuron projection
• Molecular function: protein binding