DDHD1

DDHD domain containing 1

Basic information

Region (hg38): 14:53036745-53153323

Previous symbols: [ "SPG28" ]

Links

ENSG00000100523

∙ NCBI:80821 ∙ OMIM:614603 ∙ HGNC:19714 ∙ Uniprot:Q8NEL9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary spastic paraplegia 28 (Moderate), mode of inheritance: AR
hereditary spastic paraplegia 28 (Supportive), mode of inheritance: AR
hereditary spastic paraplegia 28 (Strong), mode of inheritance: AR
hereditary spastic paraplegia 28 (Definitive), mode of inheritance: AR
hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 28, autosomal recessive	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	Neurologic	15786464; 23176821

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDHD1 gene.

Hereditary_spastic_paraplegia_28 (368 variants)
Inborn_genetic_diseases (113 variants)
not_provided (97 variants)
Hereditary_spastic_paraplegia (27 variants)
not_specified (23 variants)
DDHD1-related_disorder (8 variants)
Spasticity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDHD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001160148.2. 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		1 clinvar	3 clinvar	108 clinvar	2 clinvar	114
missense	1 clinvar	1 clinvar	244 clinvar	11 clinvar	2 clinvar	259
nonsense	5 clinvar	1 clinvar	1 clinvar			7
start loss			1			1
frameshift	16 clinvar	2 clinvar	1 clinvar			19
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	23	6	250	119	4

Highest pathogenic variant AF is 0.000042135474

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDHD1	protein_coding	protein_coding	ENST00000323669	13	109315

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.902	0.0980	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	427	501	0.852	0.0000251	5836
Missense in Polyphen		107	159.92	0.66909		1863
Synonymous	-0.246	198	194	1.02	0.00000959	1760
Loss of Function	4.93	8	42.8	0.187	0.00000234	500

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000261	0.000261
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000201	0.000185
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Phospholipase that hydrolyzes phosphatidic acid, including 1,2-dioleoyl-sn-phosphatidic acid. The different isoforms may change the substrate specificity. {ECO:0000269|PubMed:22922100}.;
Pathway: Metabolism of lipids;Metabolism;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PA (Consensus)

Recessive Scores

pRec: 0.106

Intolerance Scores

loftool: 0.0380
rvis_EVS: -0.07
rvis_percentile_EVS: 48.78

Haploinsufficiency Scores

pHI: 0.395
hipred: Y
hipred_score: 0.563
ghis: 0.580

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ddhd1
Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; skeleton phenotype; reproductive system phenotype; hematopoietic system phenotype; immune system phenotype;

Gene ontology

Biological process: lipid catabolic process;positive regulation of mitochondrial fission
Cellular component: cytosol
Molecular function: phospholipase activity;protein binding;metal ion binding