HYDIN

Summary

HYDIN (HYDIN axonemal central pair apparatus protein, HGNC:19368) is a protein-coding gene on chromosome 16q22.2, encoding Hydrocephalus-inducing protein homolog (Q4G0P3). Required for ciliary motility.

This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1.

Source: NCBI Gene 54768 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 5 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 631 total — 21 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 60
• MANE Select transcript: NM_001270974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19368
Approved symbol	HYDIN
Name	HYDIN axonemal central pair apparatus protein
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434D0513, KIAA1864, PPP1R31, CILD5
Ensembl gene	ENSG00000157423
Ensembl biotype	protein_coding
OMIM	610812
Entrez	54768

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 10 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000288168, ENST00000309900, ENST00000321489, ENST00000378856, ENST00000393552, ENST00000393567, ENST00000536785, ENST00000537789, ENST00000538248, ENST00000538382, ENST00000538568, ENST00000539447, ENST00000539973, ENST00000540892, ENST00000541601, ENST00000542283, ENST00000542890, ENST00000543521, ENST00000543639, ENST00000545230, ENST00000545267, ENST00000546257, ENST00000546297

RefSeq mRNA: 4 — MANE Select: NM_001270974 NM_001198542, NM_001198543, NM_001270974, NM_017558

CCDS: CCDS10897, CCDS56004, CCDS56005, CCDS59269

Canonical transcript exons

ENST00000393567 — 86 exons

Exon	Start	End
ENSE00001313157	70802084	70808062
ENSE00002202981	70882660	70882895
ENSE00002207144	70991318	70991396
ENSE00002209141	70872037	70872179
ENSE00002214549	70879605	70879756
ENSE00002215202	71184865	71184990
ENSE00002216625	70981391	70981568
ENSE00002218546	70883920	70884124
ENSE00002219114	70952421	70952635
ENSE00002220387	71175607	71175741
ENSE00002235633	70891646	70891884
ENSE00002242241	70892361	70892529
ENSE00002246919	71018129	71018442
ENSE00002253276	70879297	70879486
ENSE00002259149	70866169	70866329
ENSE00002261374	70985185	70985322
ENSE00002262197	70874817	70874919
ENSE00002266608	70918211	70918429
ENSE00002267524	70943812	70943949
ENSE00002270788	71025383	71025526
ENSE00002278057	70975136	70975269
ENSE00002283759	70889587	70889704
ENSE00002288159	70868570	70868788
ENSE00002295852	70894449	70894548
ENSE00002296727	70978914	70979041
ENSE00002304250	70974534	70974670
ENSE00002312270	70874305	70874592
ENSE00002316946	71178928	71179047
ENSE00002318785	70992070	70992210
ENSE00003462456	71088301	71088524
ENSE00003468098	70901004	70901202
ENSE00003468138	70973829	70974020
ENSE00003473494	71152659	71152783
ENSE00003474563	70959647	70959820
ENSE00003478511	70935952	70936114
ENSE00003484142	71062169	71062333
ENSE00003487717	71020174	71020317
ENSE00003491338	70837690	70837888
ENSE00003518058	70833887	70834164
ENSE00003525301	70895981	70896080
ENSE00003531252	70974173	70974300
ENSE00003533868	70973343	70973492
ENSE00003535201	70907372	70907491
ENSE00003535571	70964728	70964896
ENSE00003540934	71137151	71137352
ENSE00003542637	71115696	71115795
ENSE00003550612	70908252	70908434
ENSE00003551871	71067290	71067390
ENSE00003551991	71031679	71031917
ENSE00003562484	70908653	70908861
ENSE00003568646	70850448	70850655
ENSE00003568836	70832848	70833067
ENSE00003580921	71079885	71079952
ENSE00003584916	71162531	71162730
ENSE00003586644	70938614	70938755
ENSE00003590450	71027602	71027875
ENSE00003594518	70970520	70970759
ENSE00003597579	70903905	70904064
ENSE00003598929	70988393	70988512
ENSE00003600308	71069267	71069502
ENSE00003601385	71093817	71093935
ENSE00003605812	70920591	70921217
ENSE00003610734	70827261	70827411
ENSE00003613839	70809783	70810007
ENSE00003615588	71129640	71129823
ENSE00003622368	71064705	71064840
ENSE00003627349	70987924	70988133
ENSE00003638532	70828266	70828429
ENSE00003642551	70903625	70903797
ENSE00003647132	70863085	70863182
ENSE00003649626	71060504	71060656
ENSE00003650583	70941636	70941819
ENSE00003651991	70860068	70860206
ENSE00003654068	71186761	71186918
ENSE00003670670	70849726	70849947
ENSE00003671488	70840064	70840233
ENSE00003672331	70955375	70955548
ENSE00003675992	70829618	70829830
ENSE00003676498	70961959	70962138
ENSE00003678828	70835676	70835834
ENSE00003682397	70857705	70857870
ENSE00003682725	70860689	70860901
ENSE00003684707	70862048	70862255
ENSE00003686789	70855128	70855275
ENSE00003690659	70818342	70818572
ENSE00003847814	71230562	71230722

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 95.35.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6040 / max 110.1672, expressed in 371 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157995	1.6040	371

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.28	gold quality
corpus callosum	UBERON:0002336	88.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.60	gold quality
pituitary gland	UBERON:0000007	80.88	gold quality
testis	UBERON:0000473	80.88	gold quality
adenohypophysis	UBERON:0002196	80.75	gold quality
fallopian tube	UBERON:0003889	80.11	gold quality
left testis	UBERON:0004533	80.06	gold quality
right testis	UBERON:0004534	79.70	gold quality
ventricular zone	UBERON:0003053	78.98	gold quality
ganglionic eminence	UBERON:0004023	77.66	gold quality
caudate nucleus	UBERON:0001873	75.25	gold quality
cortical plate	UBERON:0005343	75.16	gold quality
nucleus accumbens	UBERON:0001882	74.93	gold quality
hypothalamus	UBERON:0001898	74.93	gold quality
Ammon’s horn	UBERON:0001954	73.65	gold quality
superior frontal gyrus	UBERON:0002661	73.43	gold quality
primary visual cortex	UBERON:0002436	72.85	gold quality
metanephros cortex	UBERON:0010533	72.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.74	gold quality
brain	UBERON:0000955	72.60	gold quality
endocervix	UBERON:0000458	72.59	gold quality
right lung	UBERON:0002167	72.08	gold quality
thyroid gland	UBERON:0002046	71.97	gold quality
amygdala	UBERON:0001876	71.71	gold quality
temporal lobe	UBERON:0001871	71.70	gold quality
right frontal lobe	UBERON:0002810	71.68	gold quality
frontal cortex	UBERON:0001870	71.35	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	6.62
E-MTAB-4850	no	0.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
GATA4	Activation

miRNA regulators (miRDB)

38 targeting HYDIN, 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-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052

Literature-anchored findings (GeneRIF, showing 9)

• We have found that the human HYDIN locus has been very recently duplicated, with a nearly identical 360-kb paralogous segment inserted on chromosome 1q21.1 (PMID:16938426)
• The results suggest frequent and coordinated adaptive immune responses against HYDIN variants in patients with cancer. (PMID:24777681)
• Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic Atrial Septal Defect (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic Atrial Septal Defect (P<5x10-4). (PMID:29505555)
• A novel homozygous nonsense HYDIN mutation in two siblings with Primary Ciliary Dyskinesia having clinical phenotype of neonatal respiratory distress, early onset persistent wet cough/nasal discharge, and consistently abnormal High speed video microscopy. (PMID:31089940)
• 41 of the 189 individuals with primary ciliary dyskinesia and situs inversus had undetectable SPEF2 and were subjected to a genetic analysis, which revealed one novel loss-of-function mutation in SPEF2 and three reported and 13 novel HYDIN mutations in 15 individuals. The remaining 25 individuals are good candidates for new, as-yet uncharacterized PCD variants that affect the CP apparatus. (PMID:31545650)
• HYDIN Variants Are a Common Cause of Primary Ciliary Dyskinesia in French Canadians. (PMID:36112114)
• Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries. (PMID:36140829)
• Novel HYDIN variants associated with male infertility in two Chinese families. (PMID:36742411)
• Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China. (PMID:38581027)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hydin	ENSMUSG00000059854
rattus_norvegicus	Hydin	ENSRNOG00000017178

Paralogs (2): DLEC1 (ENSG00000008226), CFAP47 (ENSG00000165164)

Protein

Protein identifiers

Hydrocephalus-inducing protein homolog — Q4G0P3 (reviewed: Q4G0P3)

All UniProt accessions (13): Q4G0P3, A0A087WVK9, F5GXK3, F5H8I6, F8WD03, H0YF91, H0YH52, J3KRJ6, J3KSY5, J3KTP9, J3QL30, J3QL79, J3QQJ7

UniProt curated annotations — full annotation on UniProt →

Function. Required for ciliary motility.

Subunit / interactions. Interacts with KIF9.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium axoneme. Flagellum.

Disease relevance. Ciliary dyskinesia, primary, 5 (CILD5) [MIM:608647] An autosomal recessive form of primary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD5 is characterized by early onset of a progressive decline in lung function due to an inability to clear mucus and particles from the airways. Affected individuals have recurrent infections of the sinuses, ears, airways, and lungs. Sperm motility is also decreased. Individuals with CILD5 do not have situs inversus. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (6)

UniProt ID	Names	Canonical?
Q4G0P3-1	1	yes
Q4G0P3-2	2
Q4G0P3-5	4
Q4G0P3-6	5
Q4G0P3-8	6
Q4G0P3-10	7

RefSeq proteins (4): NP_001185471, NP_001185472, NP_001257903, NP_060028 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR033305	Hydin-like	Family
IPR033768	Hydin_ADK	Domain
IPR053879	HYDIN_VesB_CFA65-like_Ig	Domain

Pfam: PF17213, PF22544

UniProt features (108 total): sequence variant 48, strand 18, splice variant 11, compositionally biased region 9, sequence conflict 9, region of interest 8, coiled-coil region 3, chain 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2E6J	SOLUTION NMR
2YS4	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q4G0P3 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_EPITHELIUM_DEVELOPMENT, chr16q22, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_TRACHEA_DEVELOPMENT, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_HEAD_DEVELOPMENT, WHN_B, GOBP_RESPIRATORY_SYSTEM_DEVELOPMENT

GO Biological Process (7): epithelial cell development (GO:0002064), cilium movement (GO:0003341), ventricular system development (GO:0021591), actin cytoskeleton organization (GO:0030036), trachea development (GO:0060438), axonemal central apparatus assembly (GO:1904158), brain development (GO:0007420)

GO Molecular Function (0):

GO Cellular Component (9): cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), axonemal central apparatus (GO:1990716), axonemal central pair projection (GO:1990718), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
animal organ development	2
epithelial cell differentiation	1
cell development	1
microtubule-based movement	1
brain development	1
system development	1
cytoskeleton organization	1
actin filament-based process	1
respiratory system development	1
cellular component assembly	1
axoneme assembly	1
central nervous system development	1
head development	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
axoneme	1
axonemal central apparatus	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cilium	1

Protein interactions and networks

STRING

1380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HYDIN	GPRIN2	O60269	914
HYDIN	SRGAP2	O75044	877
HYDIN	SRGAP3	O43295	864
HYDIN	NBPF1	Q3BBV0	861
HYDIN	DRD5	P21918	830
HYDIN	NPEPPS	P55786	829
HYDIN	UGT2B17	O75795	827
HYDIN	GTF2I	P78347	797
HYDIN	RSPH4A	Q5TD94	766
HYDIN	ASPM	Q8IZT6	752
HYDIN	RSPH9	Q9H1X1	737
HYDIN	CCDC39	Q9UFE4	727
HYDIN	CCDC40	Q4G0X9	717
HYDIN	DNAH11	Q96DT5	717
HYDIN	DNAH5	Q8TE73	715

IntAct

4 interactions, top by confidence:

A	B	Type	Score
HYDIN	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
HYDIN	PDIA3	psi-mi:“MI:0915”(physical association)	0.400
ECE1	HYDIN	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (28): HYDIN (Two-hybrid), HYDIN (Proximity Label-MS), HYDIN (Affinity Capture-MS), HYDIN (Synthetic Lethality), PEF1 (Two-hybrid), HYDIN (Proximity Label-MS), HYDIN (Affinity Capture-MS), HYDIN (Affinity Capture-MS), HYDIN (Affinity Capture-MS), HYDIN (Affinity Capture-MS), HYDIN (Protein-RNA), HYDIN (Cross-Linking-MS (XL-MS)), TBCA (Cross-Linking-MS (XL-MS)), NUDC (Cross-Linking-MS (XL-MS)), HYDIN (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: Q4G0P3, Q80W93

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HYDIN	“up-regulates quantity by expression”	GATA4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	47
Uncertain significance	333
Likely benign	170
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323082	NM_001270974.2(HYDIN):c.8008C>T (p.Gln2670Ter)	Pathogenic
1323084	NM_001270974.2(HYDIN):c.3175C>T (p.Arg1059Ter)	Pathogenic
2671841	NM_001270974.2(HYDIN):c.10949-2A>G	Pathogenic
2671844	NM_001270974.2(HYDIN):c.1797C>G (p.Tyr599Ter)	Pathogenic
3027473	NM_001270974.2(HYDIN):c.10012G>T (p.Glu3338Ter)	Pathogenic
3027482	NM_001270974.2(HYDIN):c.1147C>T (p.Arg383Ter)	Pathogenic
3027483	NM_001270974.2(HYDIN):c.4888A>T (p.Lys1630Ter)	Pathogenic
3027487	NM_001270974.2(HYDIN):c.13709del (p.Pro4570fs)	Pathogenic
3027488	NM_001270974.2(HYDIN):c.1529del (p.Phe510fs)	Pathogenic
3027494	NM_001270974.2(HYDIN):c.3252dup (p.Val1085fs)	Pathogenic
3239643	NM_001270974.2(HYDIN):c.3206_3209del (p.Lys1069fs)	Pathogenic
3898514	NM_001270974.2(HYDIN):c.9979+1G>T	Pathogenic
3901111	NM_001270974.2(HYDIN):c.1351C>T (p.Arg451Ter)	Pathogenic
3901484	NM_001270974.2(HYDIN):c.4866del (p.Pro1623fs)	Pathogenic
39699	NM_001270974.2(HYDIN):c.922A>T (p.Lys308Ter)	Pathogenic
4056784	NM_001270974.2(HYDIN):c.8674_8675delinsG (p.Gln2892fs)	Pathogenic
4073579	NM_001270974.2(HYDIN):c.2616_2617insTGGCACTGAC (p.Leu873delinsTrpHisTer)	Pathogenic
4755444	NM_001270974.2(HYDIN):c.1330C>T (p.Arg444Ter)	Pathogenic
4819537	NM_001270974.2(HYDIN):c.6491C>A (p.Ser2164Ter)	Pathogenic
65472	NM_001270974.2(HYDIN):c.3786-1G>T	Pathogenic
869381	NM_001270974.2(HYDIN):c.12530del (p.Pro4177fs)	Pathogenic
1324558	NM_001270974.2(HYDIN):c.9397C>T (p.Gln3133Ter)	Likely pathogenic
1344890	NM_001270974.2(HYDIN):c.6344_6345dup (p.Ile2116fs)	Likely pathogenic
1678091	NM_001270974.2(HYDIN):c.1030A>T (p.Arg344Ter)	Likely pathogenic
1678511	NM_001270974.2(HYDIN):c.1146_1147del (p.Arg383fs)	Likely pathogenic
1806491	NM_001270974.2(HYDIN):c.11712del (p.Gln3905fs)	Likely pathogenic
2431690	NM_001270974.2(HYDIN):c.3829_3832del (p.Leu1277fs)	Likely pathogenic
2442393	NM_001270974.2(HYDIN):c.12444-1G>A	Likely pathogenic
2584824	NM_001270974.2(HYDIN):c.13402-2A>G	Likely pathogenic
3027471	NM_001270974.2(HYDIN):c.15037_15048delinsGATGATATA (p.Tyr5013_Pro5016delinsAspAspIle)	Likely pathogenic

SpliceAI

4212 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71031721:T:C	donor_gain	1.0000
16:71031913:TGTGC:T	acceptor_gain	1.0000
16:71031914:GTGC:G	acceptor_gain	1.0000
16:71031915:TGC:T	acceptor_gain	1.0000
16:71031916:GC:G	acceptor_gain	1.0000
16:71031917:CC:C	acceptor_gain	1.0000
16:71031918:C:CC	acceptor_gain	1.0000
16:71031918:CTGCA:C	acceptor_loss	1.0000
16:71031919:T:C	acceptor_loss	1.0000
16:71060668:C:CT	acceptor_gain	1.0000
16:71062334:C:CA	acceptor_loss	1.0000
16:71062335:T:A	acceptor_loss	1.0000
16:71064700:CTCA:C	donor_loss	1.0000
16:71064701:TCACC:T	donor_loss	1.0000
16:71064702:CACC:C	donor_loss	1.0000
16:71064703:A:AC	donor_gain	1.0000
16:71064703:ACCTG:A	donor_loss	1.0000
16:71064704:C:CC	donor_gain	1.0000
16:71064856:C:CT	acceptor_gain	1.0000
16:71064856:C:T	acceptor_gain	1.0000
16:71064857:A:T	acceptor_gain	1.0000
16:71064859:C:CT	acceptor_gain	1.0000
16:71067285:AATAC:A	donor_loss	1.0000
16:71067286:ATAC:A	donor_loss	1.0000
16:71067287:TA:T	donor_loss	1.0000
16:71067289:C:CT	donor_loss	1.0000
16:71067289:CCTTG:C	donor_gain	1.0000
16:71067386:GTCAC:G	acceptor_gain	1.0000
16:71067387:TCAC:T	acceptor_gain	1.0000
16:71067388:CAC:C	acceptor_gain	1.0000

AlphaMissense

33922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:70833060:A:G	W4563R	0.999
16:70833060:A:T	W4563R	0.999
16:70901150:A:G	W2968R	0.999
16:70901150:A:T	W2968R	0.999
16:70903781:G:T	A2898D	0.999
16:70807599:A:G	L5116P	0.998
16:70807612:A:G	W5112R	0.998
16:70807612:A:T	W5112R	0.998
16:70807659:A:G	L5096P	0.998
16:70807710:A:T	V5079D	0.998
16:70828374:C:T	G4723E	0.998
16:70828375:C:A	G4723W	0.998
16:70829659:A:C	Y4691D	0.998
16:70829722:A:G	W4670R	0.998
16:70829722:A:T	W4670R	0.998
16:70882727:A:G	F3383S	0.998
16:70894475:G:C	N3074K	0.998
16:70894475:G:T	N3074K	0.998
16:70903779:A:C	Y2899D	0.998
16:70904013:G:C	N2856K	0.998
16:70904013:G:T	N2856K	0.998
16:70907396:A:G	L2831P	0.998
16:70807594:C:A	G5118W	0.997
16:70807763:G:C	F5061L	0.997
16:70807763:G:T	F5061L	0.997
16:70807764:A:G	F5061S	0.997
16:70807765:A:G	F5061L	0.997
16:70807814:A:C	N5044K	0.997
16:70807814:A:T	N5044K	0.997
16:70828285:A:G	W4753R	0.997

dbSNP variants (sampled 300 via entrez): RS1000012886 (16:71000224 C>T), RS1000018342 (16:71198137 A>G), RS1000027540 (16:71192044 C>G), RS1000029364 (16:71098173 A>G), RS1000034965 (16:71006689 C>G), RS1000060833 (16:71152865 T>C), RS1000097670 (16:71056200 G>C), RS1000106289 (16:71006276 G>A,C), RS1000110036 (16:70854322 C>T), RS1000127863 (16:71222076 G>C), RS1000146353 (16:70907683 A>G), RS1000146901 (16:71040964 C>T), RS1000148730 (16:70839647 T>A,C), RS1000180146 (16:71077717 G>A,T), RS1000192503 (16:71028159 C>T)

Disease associations

OMIM: gene MIM:610812 | disease phenotypes: MIM:608647, MIM:244400, MIM:300755, MIM:616977

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 5	Definitive	Autosomal recessive
primary ciliary dyskinesia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
primary ciliary dyskinesia 5	Definitive	AR

Mondo (5): primary ciliary dyskinesia 5 (MONDO:0012088), breast ductal adenocarcinoma (MONDO:0005590), primary ciliary dyskinesia (MONDO:0016575), immunodeficiency disease (MONDO:0021094), intellectual disability, autosomal dominant 43 (MONDO:0014858)

Orphanet (1): Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001737_31	Chronic obstructive pulmonary disease-related biomarkers	8.000000e-06
GCST002112_13	Celiac disease	7.000000e-06
GCST004604_74	Hematocrit	5.000000e-09
GCST007268_56	Diastolic blood pressure	2.000000e-09
GCST007269_295	Pulse pressure	1.000000e-14
GCST008526_62	Coffee consumption	4.000000e-08
GCST010204_135	Low density lipoprotein cholesterol levels	1.000000e-11
GCST010243_147	Apolipoprotein B levels	9.000000e-09
GCST010245_39	LDL cholesterol levels	2.000000e-09
GCST010725_47	Malaria	6.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004811	interleukin-8 measurement
EFO:0004348	hematocrit
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006781	coffee consumption measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
C563886	Ciliary Dyskinesia, Primary, 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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	affects methylation, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Aflatoxin B1	increases methylation, decreases methylation	2
terbufos	increases methylation	1
butyraldehyde	increases expression	1
benzo(e)pyrene	affects methylation	1
cyfluthrin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Chlorpyrifos	decreases expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Methapyrilene	affects methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00000118	PHASE3	COMPLETED	Ganciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134	PHASE3	COMPLETED	Studies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590	PHASE3	COMPLETED	Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267	PHASE3	COMPLETED	A Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183	PHASE3	COMPLETED	A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568	PHASE3	WITHDRAWN	Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231	PHASE3	COMPLETED	Multicenter, Safety Study Of Maraviroc
NCT00523211	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334	PHASE3	COMPLETED	Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160	PHASE3	COMPLETED	CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011	PHASE3	COMPLETED	Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569	PHASE3	COMPLETED	Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults