HCFC1
host cell factor C1, the group of NSL histone acetyltransferase complex|Protein phosphatase 1 regulatory subunits|ATAC complex
Basic information
Region (hg38): X:153947557-153971818
Previous symbols: [ "HFC1", "MRX3" ]
Links
Phenotypes
GenCC
Source:
- methylmalonic acidemia with homocystinuria, type cblX (Moderate), mode of inheritance: XL
- non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
- methylmalonic acidemia with homocystinuria, type cblX (Supportive), mode of inheritance: XL
- X-linked intellectual disability (Definitive), mode of inheritance: XL
- methylmalonic acidemia with homocystinuria, type cblX (Definitive), mode of inheritance: XL
- methylmalonic acidemia with homocystinuria, type cblX (Strong), mode of inheritance: XL
- X-linked intellectual disability (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Methylmalonic aciduria and homocysteinemia, cblX type | XL | Biochemical | Medical interventions (eg, cofactor therapy with injectable hydroxycobalamin) and dietary management (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) may be to beneficial in both acute and chronic states | Biochemical; Neurologic | 24011988 |
ClinVar
This is a list of variants' phenotypes submitted to
- Methylmalonic_acidemia_with_homocystinuria,_type_cblX (1121 variants)
- not_provided (295 variants)
- not_specified (135 variants)
- Inborn_genetic_diseases (114 variants)
- HCFC1-related_disorder (36 variants)
- Intellectual_disability (6 variants)
- Disorders_of_Intracellular_Cobalamin_Metabolism (6 variants)
- X-linked_intellectual_disability (2 variants)
- See_cases (1 variants)
- Cobalamin_C_disease (1 variants)
- Autosomal_recessive_disease (1 variants)
- Genetic_developmental_and_epileptic_encephalopathy (1 variants)
- HCFC1-related_disorders (1 variants)
- Kabuki_syndrome_1 (1 variants)
- Neurodevelopmental_abnormality (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCFC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005334.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 500 | 137 | 645 | |||
| missense | 322 | 115 | 11 | 459 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 7 | 8 | 331 | 616 | 148 |
Highest pathogenic variant AF is 0.00000192225
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HCFC1 | protein_coding | protein_coding | ENST00000310441 | 26 | 24255 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.86e-8 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.63 | 419 | 893 | 0.469 | 0.0000774 | 12925 |
| Missense in Polyphen | 218 | 598.05 | 0.36452 | 8637 | ||
| Synonymous | -2.08 | 477 | 423 | 1.13 | 0.0000421 | 4642 |
| Loss of Function | 6.50 | 0 | 49.2 | 0.00 | 0.00000349 | 769 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655}.;
- Disease
- DISEASE: Mental retardation, X-linked 3 (MRX3) [MIM:309541]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:23000143}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Herpes simplex infection - Homo sapiens (human);Mitochondrial Gene Expression;Post-translational protein modification;Metabolism of proteins;Chromatin modifying enzymes;HATs acetylate histones;UCH proteinases;Deubiquitination;Chromatin organization;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.158
Intolerance Scores
- loftool
- 0.00303
- rvis_EVS
- -1.46
- rvis_percentile_EVS
- 3.86
Haploinsufficiency Scores
- pHI
- 0.358
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.560
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.833
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hcfc1
- Phenotype
- embryo phenotype; liver/biliary 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); growth/size/body region phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- hcfc1b
- Affected structure
- neuronal stem cell
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;blastocyst hatching;regulation of transcription, DNA-templated;mitochondrion organization;cell cycle;positive regulation of gene expression;protein deubiquitination;release from viral latency;regulation of protein complex assembly;histone H4-K5 acetylation;histone H4-K8 acetylation;histone H4-K16 acetylation;positive regulation of cell cycle;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;protein stabilization;cellular response to organic cyclic compound
- Cellular component
- histone acetyltransferase complex;nucleus;nucleoplasm;Ada2/Gcn5/Ada3 transcription activator complex;cytoplasm;membrane;axon;dendrite;protein-containing complex;neuronal cell body;Set1C/COMPASS complex;SAGA-type complex;MLL1 complex
- Molecular function
- DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;transcription coactivator activity;protein binding;protein binding, bridging;activating transcription factor binding;identical protein binding;histone acetyltransferase activity (H4-K5 specific);histone acetyltransferase activity (H4-K8 specific);cadherin binding;histone acetyltransferase activity (H4-K16 specific);sequence-specific double-stranded DNA binding