HDHD5

Summary

HDHD5 (haloacid dehalogenase like hydrolase domain containing 5, HGNC:1843) is a protein-coding gene on chromosome 22q11.1, encoding Haloacid dehalogenase-like hydrolase domain-containing 5 (Q9BXW7).

Predicted to be involved in glycerophospholipid biosynthetic process. Located in mitochondrion.

Source: NCBI Gene 27440 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 108 total
• Druggable target: yes
• MANE Select transcript: NM_033070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1843
Approved symbol	HDHD5
Name	haloacid dehalogenase like hydrolase domain containing 5
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000069998
Ensembl biotype	protein_coding
Entrez	27440

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000155674, ENST00000336737, ENST00000399852, ENST00000463033, ENST00000477157, ENST00000480451, ENST00000486462, ENST00000895142, ENST00000895143, ENST00000895144, ENST00000895145, ENST00000895146, ENST00000895147, ENST00000895148, ENST00000930003, ENST00000930004, ENST00000930005, ENST00000930006, ENST00000930007, ENST00000930008, ENST00000930009, ENST00000969828

RefSeq mRNA: 2 — MANE Select: NM_033070 NM_017829, NM_033070

CCDS: CCDS13741, CCDS33595

Canonical transcript exons

ENST00000336737 — 8 exons

Exon	Start	End
ENSE00000650236	17143098	17143131
ENSE00000650240	17145024	17145117
ENSE00000879002	17159126	17159277
ENSE00001888325	17137520	17138357
ENSE00003579586	17141059	17141233
ENSE00003590818	17148448	17148560
ENSE00003611649	17138550	17138738
ENSE00003684102	17149542	17149745

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 95.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0107 / max 210.4541, expressed in 1800 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193070	20.5729	1793
193069	1.6120	1079
193068	1.3227	910
193066	0.2672	124
193067	0.2359	88

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.61	gold quality
heart left ventricle	UBERON:0002084	93.23	gold quality
cardiac ventricle	UBERON:0002082	93.03	gold quality
right lobe of liver	UBERON:0001114	92.37	gold quality
pancreatic ductal cell	CL:0002079	92.26	silver quality
mucosa of transverse colon	UBERON:0004991	92.07	gold quality
gastrocnemius	UBERON:0001388	91.74	gold quality
right adrenal gland	UBERON:0001233	91.72	gold quality
right adrenal gland cortex	UBERON:0035827	91.56	gold quality
left adrenal gland	UBERON:0001234	91.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.34	gold quality
monocyte	CL:0000576	91.32	gold quality
parotid gland	UBERON:0001831	91.30	gold quality
mononuclear cell	CL:0000842	91.21	gold quality
muscle of leg	UBERON:0001383	91.18	gold quality
left adrenal gland cortex	UBERON:0035825	91.13	gold quality
cortical plate	UBERON:0005343	91.06	gold quality
leukocyte	CL:0000738	91.05	gold quality
heart	UBERON:0000948	90.92	gold quality
adrenal cortex	UBERON:0001235	90.79	gold quality
right atrium auricular region	UBERON:0006631	90.58	gold quality
lower esophagus mucosa	UBERON:0035834	90.56	gold quality
ventricular zone	UBERON:0003053	90.50	gold quality
muscle organ	UBERON:0001630	90.28	gold quality
skeletal muscle organ	UBERON:0014892	90.28	gold quality
granulocyte	CL:0000094	90.17	gold quality
transverse colon	UBERON:0001157	90.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.04	gold quality
adrenal gland	UBERON:0002369	89.96	gold quality
skin of abdomen	UBERON:0001416	89.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.11
E-MTAB-6142	no	148.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting HDHD5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6760-3P	96.35	68.31	1001
HSA-MIR-2114-5P	96.00	64.56	617

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdhd5	ENSDARG00000105077
mus_musculus	Hdhd5	ENSMUSG00000058979
rattus_norvegicus	Hdhd5	ENSRNOG00000011338
caenorhabditis_elegans		WBGENE00019255

Paralogs (1): CRLS1 (ENSG00000088766)

Protein

Protein identifiers

Haloacid dehalogenase-like hydrolase domain-containing 5 — Q9BXW7 (reviewed: Q9BXW7)

Alternative names: Cat eye syndrome critical region protein 5

All UniProt accessions (2): Q9BXW7, A8MYZ9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed.

Miscellaneous. Candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2. Duplication usually takes in the form of a surpernumerary bisatellited isodicentric chromosome, resulting in four copies of the region (represents an inv dup(22)(q11)). CES is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development.

Similarity. Belongs to the HAD-like hydrolase superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BXW7-1	2	yes
Q9BXW7-2	1

RefSeq proteins (2): NP_060299, NP_149061* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006353	HAD-SF_hydro_IIA_CECR5	Family
IPR006357	HAD-SF_hydro_IIA	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR050324	CDP-alcohol_PTase-I	Family

Pfam: PF13344

UniProt features (9 total): sequence variant 3, sequence conflict 3, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXW7-F1	84.64	0.65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, PARENT_MTOR_SIGNALING_UP, GRYDER_PAX3FOXO1_TOP_ENHANCERS, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN

GO Biological Process (1): glycerophospholipid biosynthetic process (GO:0046474)

GO Molecular Function (0):

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid metabolic process	1
phospholipid biosynthetic process	1
glycerolipid biosynthetic process	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDHD5	D6RC18	D6RC18	683
HDHD5	ISY1	Q9ULR0	656
HDHD5	EFCC1	Q9HA90	571
HDHD5	TCEANC2	Q96MN5	566
HDHD5	TMEM121B	Q9BXQ6	547
HDHD5	CECR2	Q9BXF3	538
HDHD5	LRRC38	Q5VT99	491
HDHD5	RAB43	Q86YS6	463
HDHD5	DUSP18	Q8NEJ0	456
HDHD5	DUSP21	Q9H596	418
HDHD5	UQCRC1	P31930	411
HDHD5	PPM1K	Q8N3J5	406
HDHD5	NOP16	Q9Y3C1	398
HDHD5	ZNF414	Q96IQ9	397
HDHD5	FAM124A	Q86V42	384

IntAct

75 interactions, top by confidence:

A	B	Type	Score
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
PDK3	PDHX	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	NAP1L4	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
HDHD5	SLC25A5	psi-mi:“MI:0914”(association)	0.350
MAIP1	TIMM44	psi-mi:“MI:0914”(association)	0.350
	NUDT19	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): CECR5 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), TIMM44 (Affinity Capture-MS), PMPCB (Affinity Capture-MS), PDK3 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), PMPCA (Affinity Capture-MS), MSRB2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), CECR5 (Affinity Capture-MS), CECR5 (Proximity Label-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, A1L504, A6NH21, A8WCG0, B0BNG2, F1RMN2, O43292, O75908, O76062, O77759, O88496, O88908, O89109, P38435, Q07175, Q0P4Y8, Q49LS0, Q5KR61, Q5RF50, Q5XK03, Q5ZKZ9, Q643R3, Q658P3, Q6MG14, Q6NVG1, Q767L9, Q7TN60, Q7TPN3, Q7TQM4, Q7ZWN0, Q8BKF1, Q8C3X8, Q8IUH8, Q8IZY2, Q8N130, Q8VC65, Q8WMV1, Q91YD1, Q9BU23

Diamond homologs: P0DKC3, P0DKC4, P46351, P94526, Q9BXW7, O13899, Q91WM2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

108 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1891 predictions. Top by Δscore:

Variant	Effect	Δscore
22:17138372:C:CT	acceptor_gain	1.0000
22:17138372:C:T	acceptor_gain	1.0000
22:17138377:C:T	acceptor_gain	1.0000
22:17138544:GCCTA:G	donor_loss	1.0000
22:17138545:CCTA:C	donor_loss	1.0000
22:17138546:CTA:C	donor_loss	1.0000
22:17138547:TACC:T	donor_loss	1.0000
22:17138548:A:AC	donor_gain	1.0000
22:17138548:AC:A	donor_gain	1.0000
22:17138548:ACC:A	donor_gain	1.0000
22:17138549:C:CC	donor_gain	1.0000
22:17138549:CC:C	donor_gain	1.0000
22:17138549:CCC:C	donor_gain	1.0000
22:17138549:CCCCA:C	donor_gain	1.0000
22:17138566:T:TA	donor_gain	1.0000
22:17138736:AACC:A	acceptor_loss	1.0000
22:17138737:ACC:A	acceptor_loss	1.0000
22:17138739:C:CA	acceptor_loss	1.0000
22:17138739:C:CC	acceptor_gain	1.0000
22:17138740:T:A	acceptor_loss	1.0000
22:17138743:C:CT	acceptor_gain	1.0000
22:17138744:A:T	acceptor_gain	1.0000
22:17141232:CCCTT:C	acceptor_gain	1.0000
22:17143132:C:CC	acceptor_gain	1.0000
22:17148446:ACC:A	donor_gain	1.0000
22:17148447:CCC:C	donor_gain	1.0000
22:17138368:C:CT	acceptor_gain	0.9900
22:17138369:A:T	acceptor_gain	0.9900
22:17138374:C:CT	acceptor_gain	0.9900
22:17138377:C:CT	acceptor_gain	0.9900

AlphaMissense

2729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:17141204:A:G	W201R	0.998
22:17141204:A:T	W201R	0.998
22:17149602:A:C	N90K	0.996
22:17149602:A:T	N90K	0.996
22:17141059:C:A	R249M	0.995
22:17141059:C:G	R249T	0.994
22:17141110:A:T	V232D	0.994
22:17141202:C:A	W201C	0.994
22:17141202:C:G	W201C	0.994
22:17145109:A:G	F151S	0.994
22:17138720:A:C	F255L	0.993
22:17138720:A:T	F255L	0.993
22:17138722:A:G	F255L	0.993
22:17141084:A:G	W241R	0.993
22:17141084:A:T	W241R	0.993
22:17141092:T:G	D238A	0.993
22:17141100:G:C	S235R	0.993
22:17141100:G:T	S235R	0.993
22:17141102:T:G	S235R	0.993
22:17149606:G:A	T89I	0.993
22:17138648:T:A	K279N	0.992
22:17138648:T:G	K279N	0.992
22:17138653:C:G	G278R	0.992
22:17138709:A:G	L259P	0.992
22:17138713:A:G	C258R	0.992
22:17138721:A:G	F255S	0.992
22:17138727:C:T	G253D	0.992
22:17141092:T:C	D238G	0.992
22:17141191:A:G	L205P	0.992
22:17149575:T:A	K99N	0.992

dbSNP variants (sampled 300 via entrez): RS1000301687 (22:17153101 G>C), RS1000311689 (22:17146215 C>T), RS1000392545 (22:17158717 TG>T), RS1000410784 (22:17154807 C>T), RS1000616349 (22:17146074 C>T), RS1000669755 (22:17140880 A>G), RS1001097445 (22:17162677 T>G), RS1001149751 (22:17162326 A>C), RS1001325462 (22:17157825 A>G), RS1001674670 (22:17139704 C>T), RS1001708857 (22:17139486 C>T), RS1001928516 (22:17156644 C>T), RS1002101704 (22:17161229 G>A,C), RS1002157051 (22:17161006 G>A,C), RS1002347691 (22:17150545 G>A,C,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002701_8	Verbal declarative memory	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066395 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651100	Binding	Binding affinity to human CECR5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2YM	Abcam HEK293T HDHD5 KO	Transformed cell line	Female
CVCL_SI69	HAP1 CECR5 (-) 1	Cancer cell line	Male
CVCL_XM70	HAP1 CECR5 (-) 2	Cancer cell line	Male
CVCL_XM71	HAP1 CECR5 (-) 3	Cancer cell line	Male
CVCL_XM72	HAP1 CECR5 (-) 4	Cancer cell line	Male
CVCL_XM73	HAP1 CECR5 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.