DOHH

deoxyhypusine hydroxylase, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 19:3490821-3500674

Previous symbols: [ "HLRC1" ]

Links

ENSG00000129932

∙ NCBI:83475 ∙ OMIM:611262 ∙ HGNC:28662 ∙ Uniprot:Q9BU89 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment (Limited), mode of inheritance: AR
neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	35858628

ClinVar

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

not_specified (51 variants)
Neurodevelopmental_disorder_with_microcephaly,_cerebral_atrophy,_and_visual_impairment (13 variants)
not_provided (9 variants)
DOHH_related_neurodevelopmental_disorder (8 variants)
DOHH-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOHH gene is commonly pathogenic or not. These statistics are base on transcript: NM_001145165.2. 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				5 clinvar		5
missense	2 clinvar	1 clinvar	57 clinvar	1 clinvar		61
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	3	58	6	0

Highest pathogenic variant AF is 0.0010003732

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOHH	protein_coding	protein_coding	ENST00000427575	4	10120

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0160	0.892	125716	0	7	125723	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.941	152	188	0.807	0.0000140	1862
Missense in Polyphen		46	68.985	0.66681		719
Synonymous	0.789	84	93.7	0.896	0.00000804	649
Loss of Function	1.41	4	8.43	0.474	4.18e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000539	0.0000528
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)- L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. This is the second step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine (PubMed:16533814, PubMed:16371467, PubMed:19706422). Hypusination is unique to mature eIF-5A factor and is essential for its function (By similarity). {ECO:0000250|UniProtKB:Q99LN9, ECO:0000255|HAMAP-Rule:MF_03101, ECO:0000269|PubMed:16371467, ECO:0000269|PubMed:16533814, ECO:0000269|PubMed:19706422}.;
Pathway: Post-translational protein modification;Metabolism of proteins;Gamma carboxylation, hypusine formation and arylsulfatase activation;hypusine biosynthesis;Hypusine synthesis from eIF5A-lysine (Consensus)

Recessive Scores

pRec: 0.149

Haploinsufficiency Scores

pHI: 0.319
hipred: N
hipred_score: 0.495
ghis: 0.596

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.576

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dohh
Phenotype: growth/size/body region phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; hematopoietic 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); renal/urinary system phenotype;

Gene ontology

Biological process: peptidyl-lysine modification to peptidyl-hypusine;oxidation-reduction process
Cellular component: cellular_component;cytosol
Molecular function: iron ion binding;protein binding;deoxyhypusine monooxygenase activity;cofactor binding