HAL

histidine ammonia-lyase

Basic information

Region (hg38): 12:95972661-95996365

Previous symbols: [ "HIS" ]

Links

ENSG00000084110 ∙ NCBI:3034 ∙ OMIM:609457 ∙ HGNC:4806 ∙ Uniprot:P42357 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• histidinemia (Supportive), mode of inheritance: AR
• histidinemia (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Histidinemia	AR	General	The clinical relevance of the condition is unclear	Biochemical	13704885; 13863215; 4421298; 6192285; 6410118; 8669938; 15806399; 20156889
The clinical relevance of the condition is unclear

ClinVar

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

• Histidinemia (114 variants)
• Inborn genetic diseases (27 variants)
• not provided (10 variants)
• Increased histidine (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HAL 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			8	4	3	15
missense			60		2	62
nonsense			4			4
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			3	1	1	5
non coding			36	9	6	51
Total	0	0	110	13	11

Variants in HAL

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

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

Position	Type	Phenotype	Significance	ClinVar
12-95972684-C-T		Histidinemia	Uncertain significance (Jan 12, 2018)
12-95972714-G-A		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95972733-T-C		Histidinemia	Benign (Jan 13, 2018)
12-95972743-T-G		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95972823-C-T		Histidinemia	Uncertain significance (Jan 12, 2018)
12-95972873-G-T		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95972920-G-A		Histidinemia	Benign (Jan 12, 2018)
12-95972932-A-C		Histidinemia	Uncertain significance (Jan 12, 2018)
12-95972949-A-G		Histidinemia	Uncertain significance (Jan 12, 2018)
12-95972991-T-G		Histidinemia	Benign (Jan 12, 2018)
12-95973054-T-C		Histidinemia	Uncertain significance (Jun 14, 2016)
12-95973063-C-A		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973071-G-A		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973112-G-GT		Histidinemia	Uncertain significance (Jun 14, 2016)
12-95973256-A-C		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973318-A-G		Histidinemia	Likely benign (Apr 27, 2017)
12-95973396-G-A		Histidinemia	Likely benign (Jan 12, 2018)
12-95973443-C-T		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973476-G-A		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973504-A-T		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973559-A-G		Histidinemia	Uncertain significance (Jan 12, 2018)
12-95973615-C-T		Histidinemia	Likely benign (Jan 13, 2018)
12-95973629-T-C		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973677-C-T		Histidinemia	Uncertain significance (Jan 13, 2018)
12-95973685-C-A		Histidinemia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HAL	protein_coding	protein_coding	ENST00000261208	20	23704

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.50e-23	0.000876	125345	1	402	125748	0.00160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.259	388	374	1.04	0.0000234	4248
Missense in Polyphen		156	150.59	1.0359		1699
Synonymous	-0.892	153	140	1.10	0.00000889	1324
Loss of Function	0.0848	35	35.5	0.985	0.00000181	428

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0103	0.0103
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.000231	0.000231
European (Non-Finnish)	0.00154	0.00153
Middle Eastern	0.000489	0.000489
South Asian	0.000687	0.000686
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Histidinemia (HISTID) [MIM:235800]: Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids. {ECO:0000269|PubMed:15806399}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Histidine metabolism - Homo sapiens (human);Histidine Metabolism;Ammonia Recycling;Histidinemia;Amino Acid metabolism;Histidine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;histidine degradation;Histidine metabolism;Histidine degradation (Consensus)

Intolerance Scores

• loftool: 0.672
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.07

Haploinsufficiency Scores

• pHI: 0.520
• hipred: N
• hipred_score: 0.341
• ghis: 0.484

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.730

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hal
• Phenotype: renal/urinary system phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: hal
• Affected structure: hematopoietic stem cell differentiation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: histidine catabolic process;histidine catabolic process to glutamate and formamide;histidine catabolic process to glutamate and formate
• Cellular component: cytosol
• Molecular function: histidine ammonia-lyase activity