DNAH2

Summary

DNAH2 (dynein axonemal heavy chain 2, HGNC:2948) is a protein-coding gene on chromosome 17p13.1, encoding Dynein axonemal heavy chain 2 (Q9P225). As part of the axonemal inner dynein arm complex plays a central role in ciliary beat.

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).

Source: NCBI Gene 146754 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 45 (Strong, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 836 total — 6 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_020877

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2948
Approved symbol	DNAH2
Name	dynein axonemal heavy chain 2
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1503, FLJ46675
Ensembl gene	ENSG00000183914
Ensembl biotype	protein_coding
OMIM	603333
Entrez	146754

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000389173, ENST00000570791, ENST00000572933, ENST00000574518, ENST00000575105, ENST00000575498

RefSeq mRNA: 2 — MANE Select: NM_020877 NM_001303270, NM_020877

CCDS: CCDS32551, CCDS76937

Canonical transcript exons

ENST00000572933 — 86 exons

Exon	Start	End
ENSE00001291442	7824537	7824727
ENSE00001293687	7821243	7821369
ENSE00001297471	7818919	7819063
ENSE00001305864	7819209	7819408
ENSE00001307078	7823442	7823628
ENSE00001310396	7818643	7818776
ENSE00001310734	7824121	7824304
ENSE00001314431	7817290	7817415
ENSE00001318732	7807470	7807586
ENSE00001326741	7823834	7823982
ENSE00001366880	7818312	7818460
ENSE00001375597	7817790	7817856
ENSE00001380528	7816571	7816735
ENSE00001384818	7817946	7818096
ENSE00001386472	7817561	7817709
ENSE00001388996	7805252	7805393
ENSE00001390130	7807150	7807319
ENSE00001505027	7804958	7805074
ENSE00001594779	7742928	7743142
ENSE00001603896	7759791	7759938
ENSE00001606023	7799103	7799242
ENSE00001606645	7719721	7719900
ENSE00001607635	7797400	7797530
ENSE00001612530	7831390	7831541
ENSE00001613819	7764117	7764273
ENSE00001615042	7740810	7740992
ENSE00001615354	7792981	7793205
ENSE00001620483	7796464	7796652
ENSE00001621160	7831661	7831775
ENSE00001622078	7740420	7740549
ENSE00001626276	7766318	7766481
ENSE00001626793	7788086	7788244
ENSE00001629067	7797680	7797829
ENSE00001629913	7759422	7759610
ENSE00001630898	7786897	7787033
ENSE00001638840	7794254	7794358
ENSE00001646901	7798558	7798718
ENSE00001664553	7770557	7770639
ENSE00001665062	7739733	7739938
ENSE00001667776	7833071	7833221
ENSE00001668044	7727122	7727292
ENSE00001669223	7797176	7797261
ENSE00001669747	7792252	7792343
ENSE00001672911	7830300	7830491
ENSE00001684461	7770753	7770933
ENSE00001689282	7733087	7733315
ENSE00001702367	7734470	7734708
ENSE00001712906	7757091	7757237
ENSE00001713391	7801578	7801710
ENSE00001726685	7758495	7758651
ENSE00001733663	7758885	7759124
ENSE00001741824	7734183	7734293
ENSE00001749942	7791917	7792069
ENSE00001755733	7760740	7760932
ENSE00001759431	7763831	7764031
ENSE00001763080	7786124	7786342
ENSE00001764906	7786570	7786687
ENSE00001767929	7830658	7830842
ENSE00001779300	7831086	7831314
ENSE00001786293	7801878	7802017
ENSE00001790632	7804256	7804466
ENSE00001790678	7723628	7723689
ENSE00001793805	7737067	7737258
ENSE00001794834	7765391	7765565
ENSE00001794932	7787860	7787997
ENSE00001795930	7832854	7832928
ENSE00001796343	7832579	7832755
ENSE00001804381	7798157	7798324
ENSE00001806748	7792657	7792855
ENSE00002641242	7833379	7833742
ENSE00002676770	7717744	7718799
ENSE00003460788	7776024	7776149
ENSE00003491065	7767900	7768061
ENSE00003495320	7780157	7780284
ENSE00003513306	7778077	7778180
ENSE00003521146	7777446	7777634
ENSE00003533780	7771330	7771468
ENSE00003542870	7768164	7768267
ENSE00003543146	7770252	7770408
ENSE00003574343	7776779	7776889
ENSE00003599840	7774759	7774976
ENSE00003608452	7780630	7780782
ENSE00003639336	7775241	7775342
ENSE00003667446	7778280	7778469
ENSE00003668995	7779243	7779423
ENSE00003685276	7781042	7781167

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 94.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0656 / max 17.1412, expressed in 29 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159332	0.0656	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	94.63	gold quality
right uterine tube	UBERON:0001302	94.59	gold quality
bronchus	UBERON:0002185	92.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.54	gold quality
oviduct epithelium	UBERON:0004804	79.06	gold quality
caput epididymis	UBERON:0004358	77.55	gold quality
fallopian tube	UBERON:0003889	75.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.33	silver quality
epithelium of nasopharynx	UBERON:0001951	72.44	silver quality
left testis	UBERON:0004533	71.63	gold quality
right testis	UBERON:0004534	71.32	gold quality
testis	UBERON:0000473	70.05	gold quality
corpus epididymis	UBERON:0004359	68.25	gold quality
nasal cavity mucosa	UBERON:0001826	66.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.68	gold quality
left ovary	UBERON:0002119	66.15	gold quality
caudate nucleus	UBERON:0001873	65.78	gold quality
nucleus accumbens	UBERON:0001882	65.77	gold quality
endothelial cell	CL:0000115	65.30	gold quality
right lung	UBERON:0002167	63.88	gold quality
pancreatic ductal cell	CL:0002079	62.88	silver quality
right ovary	UBERON:0002118	62.76	gold quality
sperm	CL:0000019	62.41	gold quality
cerebellar hemisphere	UBERON:0002245	62.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.03	gold quality
putamen	UBERON:0001874	62.02	gold quality
cerebellar cortex	UBERON:0002129	61.96	gold quality
decidua	UBERON:0002450	61.83	gold quality
ovary	UBERON:0000992	61.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting DNAH2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-7846-3P	96.92	65.18	51
HSA-MIR-3124-5P	85.65	64.17	5

Literature-anchored findings (GeneRIF, showing 2)

• the DNAH2 mutation can cause severe sperm flagella defects that damage sperm motility. (PMID:30811583)
• Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella. (PMID:33771466)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnah2	ENSDARG00000087352
mus_musculus	Dnah2	ENSMUSG00000005237
rattus_norvegicus	Dnah2	ENSRNOG00000052688
drosophila_melanogaster	kl-2	FBGN0001313

Paralogs (15): DNAH9 (ENSG00000007174), DNAH5 (ENSG00000039139), DNAH11 (ENSG00000105877), DNAH1 (ENSG00000114841), DNAH6 (ENSG00000115423), DNAH7 (ENSG00000118997), DNAH8 (ENSG00000124721), DNAH3 (ENSG00000158486), DNAH12 (ENSG00000174844), DNHD1 (ENSG00000179532), DNAH14 (ENSG00000185842), DYNC2H1 (ENSG00000187240), DNAH17 (ENSG00000187775), DYNC1H1 (ENSG00000197102), DNAH10 (ENSG00000197653)

Protein

Protein identifiers

Dynein axonemal heavy chain 2 — Q9P225 (reviewed: Q9P225)

Alternative names: Axonemal beta dynein heavy chain 2, Ciliary dynein heavy chain 2, Dynein heavy chain domain-containing protein 3

All UniProt accessions (3): Q9P225, I3L4H9, I3L520

UniProt curated annotations — full annotation on UniProt →

Function. As part of the axonemal inner dynein arm complex plays a central role in ciliary beat. Expressed in sperm flagellum, it is required for sperm motility. Dyneins are microtubule-based molecular motors possessing ATPase activities that can convert the chemical energy of ATP into relative sliding between adjacent microtubule doublets to generate ciliary bending.

Subunit / interactions. Part of the axonemal inner dynein arm complex that consists of at least two heavy chains and a number of intermediate and light chains. Interacts with DNAI4.

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

Tissue specificity. Expressed primarily in trachea and testis, 2 tissues containing axonemal structures. Also expressed in lung. Expressed in spermatozoa (at protein level).

Disease relevance. Spermatogenic failure 45 (SPGF45) [MIM:619094] An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in severe teratozoospermia. SPGF45 is characterized by multiple morphologic abnormalities of spermatozoa flagella. Some spermatozoa also show abnormalities of the head. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.

Similarity. Belongs to the dynein heavy chain family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P225-1	1	yes
Q9P225-2	2
Q9P225-3	3

RefSeq proteins (2): NP_001290199, NP_065928* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR004273	Dhc_D6_P-loop	Domain
IPR013594	Dynein_heavy_tail	Domain
IPR013602	Dhc_linker	Domain
IPR024317	Dhc_D4	Domain
IPR024743	Dynein_HC_stalk	Domain
IPR026983	DHC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035699	Dhc_AAA	Domain
IPR035706	AAA_9	Domain
IPR041228	Dhc_C	Domain
IPR041466	Dhc_AAA5_ext	Domain
IPR041589	DNAH3_AAA_lid_1	Domain
IPR041658	AAA_lid_11	Domain
IPR042219	AAA_lid_11_sf	Homologous_superfamily
IPR042222	Dynein_2_N	Homologous_superfamily
IPR042228	Dynein_linker_3	Homologous_superfamily
IPR043157	Dynein_AAA1S	Homologous_superfamily
IPR043160	Dynein_C_barrel	Homologous_superfamily
IPR056759	DYH2-5-8_CC	Domain

Pfam: PF03028, PF08385, PF08393, PF12774, PF12775, PF12777, PF12780, PF12781, PF17852, PF17857, PF18198, PF18199, PF25007

UniProt features (54 total): sequence variant 23, region of interest 9, splice variant 6, repeat 5, binding site 4, coiled-coil region 3, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

No AlphaFold model available for Q9P225 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 1803–1810; 2084–2091; 2416–2423; 2762–2769

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_INNER_DYNEIN_ARM_ASSEMBLY, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, KEGG_HUNTINGTONS_DISEASE, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, MULLIGHAN_MLL_SIGNATURE_2_DN, GOCC_CYTOPLASMIC_REGION

GO Biological Process (4): inner dynein arm assembly (GO:0036159), cilium-dependent cell motility (GO:0060285), cilium movement involved in cell motility (GO:0060294), microtubule-based movement (GO:0007018)

GO Molecular Function (7): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), minus-end-directed microtubule motor activity (GO:0008569), dynein intermediate chain binding (GO:0045505), dynein light intermediate chain binding (GO:0051959), nucleotide binding (GO:0000166), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (12): axonemal dynein complex (GO:0005858), microtubule (GO:0005874), axoneme (GO:0005930), dynein complex (GO:0030286), motile cilium (GO:0031514), sperm flagellum (GO:0036126), inner dynein arm (GO:0036156), 9+2 motile cilium (GO:0097729), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium movement	2
ATP-dependent activity	2
protein binding	2
axonemal dynein complex assembly	1
cilium or flagellum-dependent cell motility	1
cell motility	1
cilium-dependent cell motility	1
microtubule-based process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
axoneme	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule associated complex	1
catalytic complex	1
cilium	1
9+2 motile cilium	1
axonemal dynein complex	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH2	TTC29	Q8NA56	586
DNAH2	DNAH12	Q6ZR08	580
DNAH2	CFAP43	Q8NDM7	564
DNAH2	TTC21A	Q8NDW8	554
DNAH2	CFAP44	Q96MT7	552
DNAH2	QRICH2	Q9H0J4	546
DNAH2	CFAP70	Q5T0N1	541
DNAH2	CFAP251	Q8TBY9	525
DNAH2	CFAP69	A5D8W1	522
DNAH2	ARMC2	Q8NEN0	520
DNAH2	DNAJB13	P59910	505
DNAH2	SPEF2	Q9C093	484
DNAH2	DZIP1	Q86YF9	479
DNAH2	WDR19	Q8NEZ3	477
DNAH2	DNALI1	O14645	475

IntAct

9 interactions, top by confidence:

A	B	Type	Score
H2BC21	DNAH2	psi-mi:“MI:0915”(physical association)	0.400
DNAH2	E7	psi-mi:“MI:0915”(physical association)	0.370
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ESR1		psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): DNAH2 (Affinity Capture-MS), DNAH2 (Affinity Capture-MS), DNAH2 (Affinity Capture-MS), DNAH2 (Protein-RNA), DNAH2 (Protein-RNA), DNAH2 (Proximity Label-MS), DNAH2 (Proximity Label-MS), DNAH2 (Affinity Capture-MS), DNAH2 (Protein-peptide), DNAH2 (Reconstituted Complex), DNAH2 (Negative Genetic), DNAH2 (Affinity Capture-MS), HNRNPA1 (Cross-Linking-MS (XL-MS)), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), HNRNPA3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GVH7, A2RRP1, D3YVL2, E9Q8T7, O55007, O88480, P0C6F1, P37276, P38650, Q0KK59, Q14204, Q3UHQ6, Q3UMB5, Q3V0Q1, Q4R7B1, Q5R414, Q5SQX6, Q5T0N1, Q5ZLS8, Q63164, Q63170, Q642P2, Q69Z23, Q6GYP7, Q6GYQ0, Q6ZR08, Q7L576, Q7TMB8, Q8BW94, Q8IVF4, Q8K2A7, Q8TD57, Q8TDY2, Q8TEV9, Q8WVF1, Q8WXX0, Q91XQ0, Q923J6, Q95LN2, Q96F07

Diamond homologs: E9Q8T7, F1SC07, M0R8U1, P0C6F1, P23098, P39057, Q39565, Q39575, Q39610, Q3V0Q1, Q63164, Q63170, Q69Z23, Q6ZR08, Q8BW94, Q8IVF4, Q8TD57, Q8TE73, Q8VHE6, Q8WXX0, Q91XQ0, Q923J6, Q96DT5, Q96JB1, Q9C0G6, Q9MBF8, Q9NYC9, Q9P225, Q9P2D7, Q9SMH3, Q9UFH2, P84753, O75369, P80197, P87061, Q2R2W1, Q5Z8K3, Q67UX0, Q7M3S9, Q80X90

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	623
Likely benign	97
Benign	55

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1455106	NC_000017.10:g.(?7578518)(7658855_?)del	Pathogenic
2442191	NM_020877.5(DNAH2):c.11644C>T (p.Arg3882Ter)	Pathogenic
984732	NM_020877.5(DNAH2):c.9298C>T (p.Arg3100Trp)	Pathogenic
984734	NM_020877.5(DNAH2):c.11500C>T (p.Arg3834Ter)	Pathogenic
984735	NM_020877.5(DNAH2):c.6960C>A (p.Ser2320Arg)	Pathogenic
984736	NM_020877.5(DNAH2):c.11503T>C (p.Ser3835Pro)	Pathogenic
3065711	NM_020877.5(DNAH2):c.7145+1G>A	Likely pathogenic
4845916	NM_020877.5(DNAH2):c.3817A>T (p.Lys1273Ter)	Likely pathogenic
4849407	NM_020877.5(DNAH2):c.4569T>G (p.Tyr1523Ter)	Likely pathogenic
984733	NM_020877.5(DNAH2):c.5770C>T (p.Arg1924Cys)	Likely pathogenic

SpliceAI

13859 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7731426:G:GT	donor_gain	1.0000
17:7733081:A:AG	acceptor_gain	1.0000
17:7733082:T:G	acceptor_gain	1.0000
17:7733085:A:AG	acceptor_gain	1.0000
17:7733086:G:GG	acceptor_gain	1.0000
17:7733086:GA:G	acceptor_gain	1.0000
17:7733313:CAGGT:C	donor_loss	1.0000
17:7733314:AGG:A	donor_loss	1.0000
17:7733317:T:A	donor_loss	1.0000
17:7734290:GAGA:G	donor_gain	1.0000
17:7734292:GA:G	donor_gain	1.0000
17:7734294:G:GG	donor_gain	1.0000
17:7734465:T:TA	acceptor_gain	1.0000
17:7734466:GCA:G	acceptor_loss	1.0000
17:7734467:CAGCC:C	acceptor_loss	1.0000
17:7734468:A:AC	acceptor_loss	1.0000
17:7734468:A:AG	acceptor_gain	1.0000
17:7734469:G:GG	acceptor_gain	1.0000
17:7734469:GC:G	acceptor_gain	1.0000
17:7734469:GCC:G	acceptor_gain	1.0000
17:7734469:GCCT:G	acceptor_gain	1.0000
17:7734469:GCCTC:G	acceptor_gain	1.0000
17:7734625:G:GT	donor_gain	1.0000
17:7734709:GTTT:G	donor_gain	1.0000
17:7737059:A:AG	acceptor_gain	1.0000
17:7737060:C:G	acceptor_gain	1.0000
17:7737061:T:A	acceptor_gain	1.0000
17:7737063:CCA:C	acceptor_loss	1.0000
17:7737064:CAGG:C	acceptor_loss	1.0000
17:7737065:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001844 (17:7725677 G>A), RS1000017991 (17:7716622 G>A), RS1000179103 (17:7762335 T>TC), RS1000188336 (17:7722801 C>G,T), RS1000216210 (17:7769606 C>A,T), RS1000225577 (17:7808404 T>A), RS1000236281 (17:7755894 G>C), RS1000275415 (17:7805198 G>A,T), RS1000283066 (17:7723427 C>T), RS1000324888 (17:7763879 C>T), RS1000330471 (17:7735280 G>A,C,T), RS1000348670 (17:7756231 C>A), RS1000364578 (17:7751951 G>A), RS1000479813 (17:7769279 A>G), RS1000496288 (17:7833959 G>C)

Disease associations

OMIM: gene MIM:603333 | disease phenotypes: MIM:619094, MIM:151623, MIM:609266, MIM:601086

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 45	Strong	Autosomal recessive

Mondo (3): spermatogenic failure 45 (MONDO:0033671), Li-Fraumeni syndrome (MONDO:0018875), laterality defects, autosomal dominant (MONDO:0010991)

Orphanet (2): Li-Fraumeni syndrome (Orphanet:524), Visceral heterotaxy (Orphanet:450)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST004604_28	Hematocrit	6.000000e-12
GCST004607_70	Plateletcrit	6.000000e-09
GCST004610_151	White blood cell count	8.000000e-09
GCST004615_109	Hemoglobin concentration	2.000000e-10
GCST006462_44	Uterine fibroids	3.000000e-30
GCST008522_50	Bitter alcoholic beverage consumption	2.000000e-08
GCST008839_272	Height	1.000000e-14
GCST010083_198	Hemoglobin levels	1.000000e-13
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST90002383_60	Hematocrit	7.000000e-25
GCST90002384_403	Hemoglobin	7.000000e-22
GCST90002396_608	Mean reticulocyte volume	3.000000e-09
GCST90002402_437	Platelet count	8.000000e-13
GCST90002403_346	Red blood cell count	4.000000e-10
GCST90002403_347	Red blood cell count	3.000000e-19
GCST90002407_572	White blood cell count	1.000000e-10
GCST90013663_65	Alanine aminotransferase levels	2.000000e-09
GCST90013664_95	Aspartate aminotransferase levels	8.000000e-14

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0007985	platelet crit
EFO:0004509	hemoglobin measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004346	neuroimaging measurement
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016864	Li-Fraumeni Syndrome	C04.700.600; C16.320.700.600; C18.452.284.520
C563391	Laterality Defects, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
afimoxifene	decreases response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
Cytarabine	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Fluorouracil	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Triclosan	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01464086	PHASE3	COMPLETED	LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome)
NCT06088030	PHASE2	RECRUITING	Arsenic Trioxide Combined With Chemotherapy for the Treatment of p53-mutated Pediatric Cancer
NCT01981525	PHASE1	COMPLETED	A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
NCT00406445	Not specified	COMPLETED	Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome
NCT01143454	Not specified	RECRUITING	Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System
NCT01443468	Not specified	RECRUITING	Clinical and Genetic Studies of Li-Fraumeni Syndrome
NCT01737255	Not specified	COMPLETED	Magnetic Resonance Imaging Screening in Li Fraumeni Syndrome
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02950987	Not specified	ACTIVE_NOT_RECRUITING	Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03176836	Not specified	ENROLLING_BY_INVITATION	Li-Fraumeni Syndrome Imaging Study
NCT04367246	Not specified	RECRUITING	Li-Fraumeni Syndrome/TP53 Biobank
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04966923	Not specified	COMPLETED	Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53
NCT04982744	Not specified	RECRUITING	Registry of Li Fraumeni and Li Fraumeni Like Syndromes
NCT05126810	Not specified	RECRUITING	Willingness to Participate in a Trial Comparing Standard Genetic Counseling Versus Personalized Genetic Counseling
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT06712095	Not specified	RECRUITING	Video Capsule Examination in Patients With Lynch Syndrome
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07032922	Not specified	COMPLETED	Exploring How to Adapt an Evidence-Based Mindful Self-Compassion Program for Young Adults With Li-Fraumeni Syndrome