SPEF2

Summary

SPEF2 (sperm flagellar and cilia associated 2, HGNC:26293) is a protein-coding gene on chromosome 5p13.2, encoding Sperm flagellar protein 2 (Q9C093). Required for correct axoneme development in spermatozoa.

Involved in sperm axoneme assembly. Located in cytosol; nuclear body; and sperm flagellum. Implicated in spermatogenic failure 43.

Source: NCBI Gene 79925 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 439 total — 9 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 52
• MANE Select transcript: NM_024867

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26293
Approved symbol	SPEF2
Name	sperm flagellar and cilia associated 2
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KPL2, FLJ23577, CT122
Ensembl gene	ENSG00000152582
Ensembl biotype	protein_coding
OMIM	610172
Entrez	79925

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000282469, ENST00000356031, ENST00000440995, ENST00000502454, ENST00000503074, ENST00000504054, ENST00000505088, ENST00000505847, ENST00000506526, ENST00000508817, ENST00000509059, ENST00000510777, ENST00000513078, ENST00000635995, ENST00000637061, ENST00000637569, ENST00000941715

RefSeq mRNA: 2 — MANE Select: NM_024867 NM_024867, NM_144722

CCDS: CCDS3910, CCDS43309

Canonical transcript exons

ENST00000356031 — 37 exons

Exon	Start	End
ENSE00001006043	35644355	35644525
ENSE00001006045	35654540	35654726
ENSE00001006046	35659019	35659207
ENSE00001006048	35646667	35646807
ENSE00001082209	35641431	35641683
ENSE00001130376	35779117	35779346
ENSE00001130386	35776257	35776395
ENSE00001130390	35773893	35774021
ENSE00001130399	35771609	35771756
ENSE00001130406	35763522	35763702
ENSE00001130413	35753624	35753761
ENSE00001130427	35739919	35740046
ENSE00001209603	35759568	35759719
ENSE00001209607	35740129	35740267
ENSE00001293491	35712812	35712886
ENSE00001296780	35697690	35697793
ENSE00001312748	35708948	35709121
ENSE00001313280	35727675	35727823
ENSE00001317049	35700496	35700752
ENSE00001405706	35694288	35694363
ENSE00003494196	35792340	35792446
ENSE00003505681	35807131	35807253
ENSE00003508995	35695735	35695796
ENSE00003521202	35667072	35667259
ENSE00003532162	35670059	35670227
ENSE00003539092	35799968	35800147
ENSE00003576520	35814464	35814611
ENSE00003584728	35795703	35795795
ENSE00003608416	35705651	35705808
ENSE00003625591	35704554	35704662
ENSE00003628949	35692570	35692724
ENSE00003644615	35649361	35649425
ENSE00003645238	35793159	35793341
ENSE00003652952	35806707	35806952
ENSE00003679866	35628460	35628562
ENSE00003684604	35691037	35691256
ENSE00003848818	35617863	35618055

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4570 / max 103.6029, expressed in 1224 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56096	4.2543	1216
56097	0.1787	75
56099	0.0240	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.88	gold quality
bronchial epithelial cell	CL:0002328	96.91	gold quality
bronchus	UBERON:0002185	95.18	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.52	gold quality
sperm	CL:0000019	90.23	gold quality
endocervix	UBERON:0000458	90.04	gold quality
calcaneal tendon	UBERON:0003701	89.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.80	gold quality
body of uterus	UBERON:0009853	87.53	gold quality
caput epididymis	UBERON:0004358	87.36	gold quality
oviduct epithelium	UBERON:0004804	86.95	gold quality
sural nerve	UBERON:0015488	86.33	gold quality
fallopian tube	UBERON:0003889	85.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.01	gold quality
left lobe of thyroid gland	UBERON:0001120	84.40	gold quality
body of pancreas	UBERON:0001150	84.23	gold quality
adenohypophysis	UBERON:0002196	84.19	gold quality
right lobe of thyroid gland	UBERON:0001119	84.02	gold quality
thyroid gland	UBERON:0002046	83.96	gold quality
pituitary gland	UBERON:0000007	83.79	gold quality
ectocervix	UBERON:0012249	83.54	gold quality
left ovary	UBERON:0002119	83.44	gold quality
epithelium of nasopharynx	UBERON:0001951	82.73	gold quality
metanephros cortex	UBERON:0010533	82.60	gold quality
right ovary	UBERON:0002118	82.39	gold quality
uterine cervix	UBERON:0000002	82.16	gold quality
buccal mucosa cell	CL:0002336	81.94	silver quality
endometrium	UBERON:0001295	81.68	gold quality
corpus epididymis	UBERON:0004359	81.68	silver quality
tibial nerve	UBERON:0001323	81.30	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	12.75
E-ANND-3	yes	10.53
E-MTAB-6058	no	233.04
E-MTAB-9801	no	2.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

74 targeting SPEF2, 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-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-370-5P	99.78	66.81	706

Literature-anchored findings (GeneRIF, showing 7)

• SPEF2 is a novel gene for human MMAF (multiple morphological abnormalities of the sperm flagella) across the populations. Functional analyses suggested that the deficiency of SPEF2 in the mutated subjects could alter the localisation of other axonemal proteins. (PMID:31048344)
• Loss-of-function mutations in the SPEF2 gene can cause the Multiple morphological abnormalities of the sperm flagella (MMAF) phenotype in human. (PMID:31151990)
• Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. (PMID:31278745)
• In individuals with primary ciliary dyskinesia and central pair defects, the CP-associated protein SPEF2 is absent in HYDIN-mutant cells. 41 of 189 individuals had undetectable SPEF2 and were subjected to a genetic analysis, which revealed one novel loss-of-function mutation in SPEF2 and 3 reported and 13 novel HYDIN mutations in 15 individuals. A mutation of SPEF2 is causative for PCD with a CP defect. (PMID:31545650)
• Mutations in SPEF2 are associated with multiple morphological abnormalities of the sperm flagella and primary ciliary dyskinesia. (PMID:31942643)
• Sperm flagellar 2 (SPEF2) is essential for sperm flagellar assembly in humans. (PMID:34755699)
• Novel SPEF2 variants cause male infertility and likely primary ciliary dyskinesia. (PMID:38568462)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spef2	ENSDARG00000098330
mus_musculus	Spef2	ENSMUSG00000072663
rattus_norvegicus	Spef2	ENSRNOG00000058275

Protein

Protein identifiers

Sperm flagellar protein 2 — Q9C093 (reviewed: Q9C093)

Alternative names: Protein KPL2

All UniProt accessions (9): A0A140VKD0, A0A1B0GWC1, A0A1B0GWD8, D6REZ4, D6RGZ5, Q9C093, H0Y8H6, H0Y989, H0YAC0

UniProt curated annotations — full annotation on UniProt →

Function. Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis. Also plays a role in bone growth where it seems to be required for normal osteoblast differentiation.

Subunit / interactions. Interacts (via C-terminus) with IFT20. Interacts with DYNC1I2.

Subcellular location. Cell projection. Cilium. Flagellum. Cytoplasm. Golgi apparatus.

Disease relevance. Spermatogenic failure 43 (SPGF43) [MIM:618751] An autosomal recessive infertility disorder characterized by asthenospermia due to multiple morphologic abnormalities of sperm flagella, including short, absent, coiled, and bent flagella. 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 (4)

UniProt ID	Names	Canonical?
Q9C093-1	1	yes
Q9C093-2	2
Q9C093-3	3
Q9C093-4	4

RefSeq proteins (2): NP_079143, NP_653323 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR010441	CH_2	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR052634	Sperm_flagellar-bone_growth	Family
IPR054517	SPEF2_D5	Domain
IPR056199	SPEF2_C	Domain

Pfam: PF00406, PF06294, PF22946, PF24082

UniProt features (37 total): sequence variant 12, compositionally biased region 7, coiled-coil region 5, splice variant 5, region of interest 5, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C093-F1	71.30	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 219 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_HEAD_DEVELOPMENT, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (7): epithelial cilium movement involved in extracellular fluid movement (GO:0003351), spermatogenesis (GO:0007283), sperm axoneme assembly (GO:0007288), skeletal system morphogenesis (GO:0048705), brain morphogenesis (GO:0048854), respiratory system development (GO:0060541), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (12): manchette (GO:0002177), extracellular region (GO:0005576), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), nuclear body (GO:0016604), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
developmental process involved in reproduction	2
animal organ morphogenesis	2
cytoplasm	2
intracellular membraneless organelle	2
cilium movement	1
extracellular transport	1
microtubule-based transport	1
male gamete generation	1
axoneme assembly	1
sperm flagellum assembly	1
skeletal system development	1
brain development	1
system development	1
cellular developmental process	1
binding	1
microtubule cytoskeleton	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
microtubule organizing center	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
nucleoplasm	1
9+2 motile cilium	1
sperm flagellum	1
cilium	1

Protein interactions and networks

STRING

1325 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPEF2	ADK	P55263	929
SPEF2	SPAG6	O75602	739
SPEF2	CFAP54	Q96N23	707
SPEF2	CFAP43	Q8NDM7	683
SPEF2	TTC21A	Q8NDW8	679
SPEF2	CFAP69	A5D8W1	668
SPEF2	IFT20	Q8IY31	666
SPEF2	ARMC2	Q8NEN0	653
SPEF2	SPAG17	Q6Q759	632
SPEF2	SPEF1	Q9Y4P9	616
SPEF2	CCDC40	Q4G0X9	607
SPEF2	CFAP70	Q5T0N1	604
SPEF2	FSIP2	Q5CZC0	603
SPEF2	DNAH1	Q9P2D7	603
SPEF2	TTC29	Q8NA56	591

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SPEF2	VIM	psi-mi:“MI:0915”(physical association)	0.400
SPEF2	MYH9	psi-mi:“MI:0915”(physical association)	0.400
SPEF2	H2BC14	psi-mi:“MI:0915”(physical association)	0.400
APOA1	CNMD	psi-mi:“MI:0914”(association)	0.350
IGHA1	PLG	psi-mi:“MI:0914”(association)	0.350
KATNAL1	CDK1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MYCBP	POTEF	psi-mi:“MI:0914”(association)	0.350
CLU	SPEF2	psi-mi:“MI:0915”(physical association)	0.000
DISC1	SPEF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): SPEF2 (Two-hybrid), SPEF2 (Protein-RNA), SPEF2 (Proximity Label-MS), SPEF2 (Proximity Label-MS), SPEF2 (Proximity Label-MS), SPEF2 (Affinity Capture-RNA), SPEF2 (Affinity Capture-MS), SPEF2 (Affinity Capture-MS), SPEF2 (Cross-Linking-MS (XL-MS)), SPEF2 (Cross-Linking-MS (XL-MS)), SPEF2 (Cross-Linking-MS (XL-MS)), PPIA (Cross-Linking-MS (XL-MS)), SPEF2 (Cross-Linking-MS (XL-MS)), SPEF2 (Cross-Linking-MS (XL-MS)), VPS45 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A087WRI3, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A6QQ68, A8E4X8, A8E5W8, A8QW39, A9JS51, D6REC4, F1P3Y5, G3X6E2, P0C875, Q0VB26, Q1MSJ5, Q2IA00, Q2T9Q3, Q2TA11, Q3UY96, Q494V2, Q497Q6, Q4KKZ1, Q4QR77, Q4R5Y0, Q4R8V8, Q5NC57, Q5ZIH9, Q6J272, Q6PII3, Q6ZQR2, Q6ZVS7, Q7Z4T9, Q8CFW7, Q8N1D5, Q8N6G2, Q8WW14, Q95LR0

Diamond homologs: A0PXW7, A1JNB1, A2BYR7, A2C4Y0, A3DJJ3, A3PF28, A4TPA4, A4W7F8, A4XLR0, A6LLN4, A6ZYI0, A7FL86, A7HM31, A8G742, A8MLG1, A8ZTL5, A9R0Q7, B0RZT0, B0U1U0, B0X5E3, B0XPW9, B1JHN1, B1XTC5, B2I757, B2K6Z6, B3LG61, B3MCQ5, B3NQ53, B4I2A8, B4KLY1, B4LP08, B4MQT3, B4PAR6, B4QBH8, B4U765, B5EFS1, B5XCA1, B6YRA7, B7IHW7, B7M3W6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	3
Uncertain significance	274
Likely benign	36
Benign	80

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
3382335	NM_024867.4(SPEF2):c.2203C>T (p.Gln735Ter)	Pathogenic
805986	NM_024867.4(SPEF2):c.13del (p.Leu5fs)	Pathogenic
805987	NM_024867.4(SPEF2):c.1745-2A>G	Pathogenic
805988	NM_024867.4(SPEF2):c.4102G>T (p.Glu1368Ter)	Pathogenic
805989	NM_024867.4(SPEF2):c.4326dup (p.Val1443fs)	Pathogenic
805990	NM_024867.4(SPEF2):c.2735del (p.Pro912fs)	Pathogenic
805991	NM_024867.4(SPEF2):c.4952del (p.Val1651fs)	Pathogenic
805992	NM_024867.4(SPEF2):c.3240del (p.Phe1080fs)	Pathogenic
870097	NM_024867.4(SPEF2):c.2507+5del	Pathogenic
2633110	NM_024867.4(SPEF2):c.3949+1G>T	Likely pathogenic
3034024	NM_024867.4(SPEF2):c.1795C>T (p.Gln599Ter)	Likely pathogenic
3780656	NM_024867.4(SPEF2):c.586C>T (p.Gln196Ter)	Likely pathogenic

SpliceAI

6693 predictions. Top by Δscore:

Variant	Effect	Δscore
5:35618047:GGACC:G	donor_gain	1.0000
5:35618048:GACCG:G	donor_gain	1.0000
5:35618056:G:GG	donor_gain	1.0000
5:35628558:AGCAG:A	donor_loss	1.0000
5:35628559:GCAG:G	donor_gain	1.0000
5:35628560:CAG:C	donor_loss	1.0000
5:35628561:AGGT:A	donor_loss	1.0000
5:35628563:G:GA	donor_loss	1.0000
5:35644496:G:GT	donor_gain	1.0000
5:35659013:TTTCA:T	acceptor_loss	1.0000
5:35659014:TTCAG:T	acceptor_loss	1.0000
5:35659015:TCA:T	acceptor_loss	1.0000
5:35659016:CAG:C	acceptor_loss	1.0000
5:35659017:A:AG	acceptor_gain	1.0000
5:35659017:A:AT	acceptor_loss	1.0000
5:35659018:G:GG	acceptor_gain	1.0000
5:35659018:GGA:G	acceptor_gain	1.0000
5:35659118:G:GT	donor_gain	1.0000
5:35659187:G:GT	donor_gain	1.0000
5:35659205:GCG:G	donor_gain	1.0000
5:35659208:G:GA	donor_loss	1.0000
5:35659208:G:GG	donor_gain	1.0000
5:35659209:T:G	donor_loss	1.0000
5:35667061:T:A	acceptor_gain	1.0000
5:35667067:TTTA:T	acceptor_loss	1.0000
5:35667068:TTA:T	acceptor_loss	1.0000
5:35667069:TA:T	acceptor_loss	1.0000
5:35667070:A:AG	acceptor_gain	1.0000
5:35667070:AG:A	acceptor_gain	1.0000
5:35667071:G:GT	acceptor_gain	1.0000

AlphaMissense

12112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:35659095:T:C	L352P	0.997
5:35654680:G:C	R311P	0.996
5:35654683:G:C	R312P	0.996
5:35691052:T:A	W514R	0.996
5:35691052:T:C	W514R	0.996
5:35659077:G:C	R346P	0.995
5:35659190:G:C	A384P	0.995
5:35740187:T:A	W1084R	0.995
5:35740187:T:C	W1084R	0.995
5:35659029:G:C	R330P	0.993
5:35659050:G:C	R337P	0.993
5:35659053:T:C	L338P	0.993
5:35659107:G:C	R356P	0.993
5:35667244:G:C	R447P	0.993
5:35670087:T:A	W462R	0.993
5:35670087:T:C	W462R	0.993
5:35740260:G:C	R1108P	0.993
5:35628549:T:C	F50L	0.992
5:35628551:T:A	F50L	0.992
5:35628551:T:G	F50L	0.992
5:35649385:T:C	F251L	0.992
5:35649387:C:A	F251L	0.992
5:35649387:C:G	F251L	0.992
5:35659170:G:C	R377P	0.992
5:35654659:G:C	R304P	0.991
5:35654678:A:C	R310S	0.991
5:35654678:A:T	R310S	0.991
5:35654718:G:C	A324P	0.991
5:35659200:G:C	R387P	0.991
5:35759581:G:C	R1161P	0.991

dbSNP variants (sampled 300 via entrez): RS1000003051 (5:35674672 A>G), RS1000014115 (5:35773873 A>G), RS1000031070 (5:35728735 T>A), RS1000039287 (5:35786646 G>A), RS1000042874 (5:35647455 G>A), RS1000096658 (5:35685147 A>G,T), RS1000117676 (5:35740624 G>A,C), RS1000120502 (5:35699181 T>G), RS1000121356 (5:35656853 G>A), RS1000129104 (5:35799311 G>A), RS1000129792 (5:35773615 C>G), RS1000141971 (5:35624761 C>A,T), RS1000166686 (5:35711563 T>C), RS1000226870 (5:35702276 C>A), RS1000236317 (5:35656582 C>T)

Disease associations

OMIM: gene MIM:610172 | disease phenotypes: MIM:618751, MIM:181500, MIM:244400

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 43	Strong	Autosomal recessive
primary ciliary dyskinesia	Supportive	Autosomal dominant
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
primary ciliary dyskinesia	Definitive	AR

Mondo (4): spermatogenic failure 43 (MONDO:0032898), schizophrenia (MONDO:0005090), primary ciliary dyskinesia (MONDO:0016575), (MONDO:0017173)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

52 total (30 of 52 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:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections
HP:0006536	Airway obstruction
HP:0008222	Female infertility

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002004_2	Adverse response to chemotherapy (neutropenia/leucopenia) (carboplatin)	2.000000e-06
GCST003219_22	Advanced age-related macular degeneration	2.000000e-08
GCST005581_3	Primary biliary cirrhosis	2.000000e-13
GCST006248_11	Response to lurasidone in schizophrenia	8.000000e-06
GCST007563_11	Allergic disease (asthma, hay fever or eczema)	3.000000e-15
GCST007564_36	Asthma or allergic disease (pleiotropy)	2.000000e-14
GCST010420_1	Pulse pressure x educational attainment (some college) interaction (2df)	7.000000e-09
GCST010726_49	Periventricular white matter hyperintensities	9.000000e-06
GCST011981_6	Homeostasis model assessment of insulin resistance	2.000000e-06
GCST012146_9	Hemoglobin levels	6.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004784	self reported educational attainment
EFO:0005763	pulse pressure measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004501	HOMA-IR
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Formaldehyde	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Gold Compounds	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression, increases abundance	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression	1
Magnetite Nanoparticles	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety