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

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.

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.

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				1		1
missense		1	26			27
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	26	1	0

Variants in DOHH

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

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

Position	Type	Phenotype	Significance	ClinVar
19-3491561-A-T		DOHH related neurodevelopmental disorder • Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	Pathogenic (Sep 30, 2022)
19-3491574-G-A		not specified	Uncertain significance (Jul 13, 2022)
19-3491582-G-A			Likely benign (Oct 01, 2024)
19-3491599-C-T		not specified	Uncertain significance (Jan 16, 2024)
19-3491625-T-A		not specified	Uncertain significance (Aug 27, 2024)
19-3491635-C-T		not specified	Uncertain significance (Nov 26, 2024)
19-3491655-A-G		DOHH related neurodevelopmental disorder • Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	Pathogenic (Sep 30, 2022)
19-3491659-C-T		not specified	Uncertain significance (Nov 09, 2021)
19-3491686-G-A		not specified	Uncertain significance (Oct 04, 2024)
19-3491688-A-C		not specified	Uncertain significance (May 31, 2023)
19-3491701-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-3491709-C-T		not specified	Uncertain significance (Aug 14, 2024)
19-3491733-G-A		Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment • DOHH related neurodevelopmental disorder	Uncertain significance (Jun 01, 2023)
19-3491739-G-A		not specified	Uncertain significance (Mar 20, 2024)
19-3491746-C-CGGTT		DOHH related neurodevelopmental disorder • Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	Pathogenic/Likely pathogenic (Jun 01, 2023)
19-3491805-T-G		not specified	Uncertain significance (Dec 14, 2023)
19-3492289-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-3492299-G-T		DOHH related neurodevelopmental disorder • Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	Pathogenic (Sep 30, 2022)
19-3492310-C-A		not specified	Uncertain significance (Apr 11, 2023)
19-3492327-C-G		not specified	Uncertain significance (Apr 23, 2024)
19-3492340-G-T		not specified	Uncertain significance (Jun 09, 2022)
19-3492346-A-T		not specified	Uncertain significance (Sep 11, 2024)
19-3492360-G-A		not specified	Uncertain significance (Nov 18, 2022)
19-3492372-C-T		not specified	Uncertain significance (Mar 28, 2022)
19-3492373-G-A		not specified	Uncertain significance (Sep 14, 2022)

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