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 56 (Definitive), mode of inheritance: AR
• 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 (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 (12 variants)
• not provided (2 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.

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	85	5	91
missense			199	4	3	206
nonsense	4					4
start loss			1			1
frameshift	10	2	1			13
inframe indel			10	3	2	15
splice donor/acceptor (+/-2bp)		1				1
splice region			9	11	1	21
non coding			4	54	34	92
Total	14	3	216	146	44

Highest pathogenic variant AF is 0.0000131

Variants in DDHD1

This is a list of pathogenic ClinVar variants found in the DDHD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-53043392-A-AGTGTGT		Hereditary spastic paraplegia	Uncertain significance (Jan 24, 2017)
14-53046607-ACTT-A			Benign (Aug 31, 2018)
14-53046611-C-CT			Likely benign (Nov 02, 2019)
14-53046634-T-C			Likely benign (Jan 28, 2019)
14-53046752-T-C			Likely benign (Jan 02, 2018)
14-53046759-CAA-C			Benign (Nov 21, 2017)
14-53046760-AAG-A		Hereditary spastic paraplegia 28	Benign (Jul 30, 2021)
14-53046773-T-C		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
14-53046775-G-A		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
14-53046778-T-A		Hereditary spastic paraplegia 28	Uncertain significance (Jul 15, 2022)
14-53046785-T-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
14-53046787-G-A		Hereditary spastic paraplegia 28	Uncertain significance (Jun 23, 2021)
14-53046803-C-G		Hereditary spastic paraplegia 28	Uncertain significance (Sep 01, 2020)
14-53046803-C-T		Hereditary spastic paraplegia 28 • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Oct 30, 2023)
14-53046804-G-A		Hereditary spastic paraplegia 28	Likely benign (Aug 28, 2023)
14-53046809-C-A		Spasticity	Uncertain significance (-)
14-53046817-T-C		Hereditary spastic paraplegia 28	Uncertain significance (Jun 13, 2022)
14-53046822-G-A		Hereditary spastic paraplegia 28	Conflicting classifications of pathogenicity (Jan 13, 2023)
14-53046867-A-G		Hereditary spastic paraplegia 28	Likely benign (Sep 08, 2023)
14-53046877-G-A		Inborn genetic diseases	Uncertain significance (Feb 02, 2024)
14-53046894-G-C		Hereditary spastic paraplegia 28	Uncertain significance (May 24, 2020)
14-53046918-G-C		not specified	Likely benign (Jul 20, 2016)
14-53046919-A-G		Hereditary spastic paraplegia 28	Uncertain significance (Aug 28, 2021)
14-53046929-CA-C		Hereditary spastic paraplegia 28	Uncertain significance (Dec 10, 2020)
14-53046945-C-T		Hereditary spastic paraplegia 28	Likely benign (Nov 22, 2022)

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