DHPS

deoxyhypusine synthase

Basic information

Region (hg38): 19:12675717-12681880

Links

ENSG00000095059 ∙ NCBI:1725 ∙ OMIM:600944 ∙ HGNC:2869 ∙ Uniprot:P49366 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with seizures and speech and walking impairment (Limited), mode of inheritance: AR
• neurodevelopmental disorder with seizures and speech and walking impairment (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with seizures and speech and walking impairment (Strong), mode of inheritance: AR
• neurodevelopmental disorder with seizures and speech and walking impairment (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with seizures and speech and walking impairment	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	Craniofacial; Musculoskeletal; Neurologic	30661771

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHPS 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				3		3
missense		1	27	1		29
nonsense			1			1
start loss			1			1
frameshift		2				2
inframe indel		1				1
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding			1			1
Total	0	5	30	4	0

Variants in DHPS

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

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

Position	Type	Phenotype	Significance	ClinVar
19-12675855-C-T		not specified	Uncertain significance (Aug 20, 2024)
19-12675874-C-T			Likely benign (Mar 01, 2025)
19-12676016-C-T		Neurodevelopmental disorder with seizures and speech and walking impairment	Conflicting classifications of pathogenicity (Oct 09, 2024)
19-12676072-C-T		not specified	Uncertain significance (Oct 20, 2024)
19-12676078-C-T		not specified	Uncertain significance (Sep 21, 2023)
19-12676091-C-T		not specified	Uncertain significance (Aug 20, 2024)
19-12676094-C-G			Uncertain significance (-)
19-12676107-T-C		not specified	Likely benign (Dec 02, 2024)
19-12676113-GATGTAA-G		Neurodevelopmental disorder with seizures and speech and walking impairment • DHPS-related disorder	Likely pathogenic (Sep 07, 2023)
19-12676124-C-T		not specified	Uncertain significance (May 28, 2024)
19-12677212-C-G			Likely pathogenic (Jun 17, 2023)
19-12677283-C-A		DHPS-related disorder	Likely benign (Dec 01, 2024)
19-12677317-G-A		not specified	Uncertain significance (Apr 20, 2024)
19-12679478-G-C		DHPS-related disorder	Benign (Dec 09, 2019)
19-12679486-G-C		not specified	Uncertain significance (Mar 29, 2023)
19-12679523-A-G		DHPS-related disorder	Benign (Dec 05, 2019)
19-12679689-A-G			Likely benign (Jan 01, 2023)
19-12679696-T-C		Neurodevelopmental disorder with seizures and speech and walking impairment • DHPS-related disorder	Pathogenic/Likely pathogenic (Oct 09, 2024)
19-12679716-G-C		not specified	Uncertain significance (Jun 06, 2023)
19-12679810-C-G		not specified	Uncertain significance (May 30, 2023)
19-12679811-C-T		not specified	Uncertain significance (Aug 02, 2023)
19-12679833-CCT-C		Neurodevelopmental disorder with seizures and speech and walking impairment	Conflicting classifications of pathogenicity (Sep 10, 2024)
19-12679860-G-A		DHPS-related disorder	Likely benign (Jul 30, 2024)
19-12679895-C-T		not specified	Uncertain significance (Dec 01, 2022)
19-12680163-T-A			Uncertain significance (Sep 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHPS	protein_coding	protein_coding	ENST00000210060	9	6186

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000163	0.972	125598	0	150	125748	0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.393	249	232	1.07	0.0000139	2423
Missense in Polyphen		85	101.98	0.8335		1082
Synonymous	-0.783	112	102	1.10	0.00000684	738
Loss of Function	1.96	9	18.0	0.500	8.60e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000681	0.000680
Ashkenazi Jewish	0.00140	0.00139
East Asian	0.000272	0.000272
Finnish	0.000509	0.000508
European (Non-Finnish)	0.000680	0.000677
Middle Eastern	0.000272	0.000272
South Asian	0.000655	0.000653
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. This is the first step of the post- translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF- 5A factor and is essential for its function.
• 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: 0.164

Intolerance Scores

• loftool: 0.918
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.267
• hipred: N
• hipred_score: 0.429
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dhps
• Phenotype: immune system phenotype; renal/urinary system phenotype; normal 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); hematopoietic system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: dhps
• Affected structure: primary islet
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: translation;spermidine metabolic process;positive regulation of cell population proliferation;peptidyl-lysine modification to peptidyl-hypusine
• Cellular component: cytoplasm;cytosol
• Molecular function: protein binding;deoxyhypusine synthase activity;identical protein binding